Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro...Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.展开更多
Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia.However,whether there is a synergistic effect between the two remains unclea...Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia.However,whether there is a synergistic effect between the two remains unclear.In this study,we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours.Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes(MSC-exos)via the tail vein and underwent 14 successive days of treadmill exercise.Neurological assessment,histopathology,and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume,evident synaptic formation and axonal regeneration,and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment.These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone.Mechanistically,further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling.These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment,which may be related to activation of the JNK1/c-Jun signaling pathway.This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.展开更多
Circular RNAs can regulate the development and progression of ischemic cerebral disease.However,it remains unclear whether they play a role in acute ischemic stroke.To investigate the role of the circular RNA Rap1b(ci...Circular RNAs can regulate the development and progression of ischemic cerebral disease.However,it remains unclear whether they play a role in acute ischemic stroke.To investigate the role of the circular RNA Rap1b(circRap1b)in acute ischemic stroke,in this study we established an in vitro model of acute ischemia and hypoxia by subjecting HT22 cells to oxygen and glucose deprivation and a mouse model of acute ischemia and hypoxia by occluding the right carotid artery.We found that circRap1b expression was remarkably down-regulated in the hippocampal tissue of the mouse model and in the HT22 cell model.In addition,Hoxa5 expression was strongly up-regulated in response to circRap1b overexpression.Hoxa5 expression was low in the hippocampus of a mouse model of acute ischemia and in HT22-AIS cells,and inhibited HT22-AIS cell apoptosis.Importantly,we found that circRap1b promoted Hoxa5 transcription by recruiting the acetyltransferase Kat7 to induce H3K14ac modification in the Hoxa5 promoter region.Hoxa5 regulated neuronal apoptosis by activating transcription of Fam3a,a neuronal apoptosis-related protein.These results suggest that circRap1b regulates Hoxa5 transcription and expression,and subsequently Fam3a expression,ultimately inhibiting cell apoptosis.Lastly,we explored the potential clinical relevance of circRap1b and Hoxa5 in vivo.Taken together,these findings demonstrate the mechanism by which circRap1b inhibits neuronal apoptosis in acute ischemic stroke.展开更多
Microglia,which are the resident macrophages of the central nervous system,are an important part of the inflammatory response that occurs after cerebral ischemia.Vav guanine nucleotide exchange factor 1(Vav1) is a gua...Microglia,which are the resident macrophages of the central nervous system,are an important part of the inflammatory response that occurs after cerebral ischemia.Vav guanine nucleotide exchange factor 1(Vav1) is a guanine nucleotide exchange factor that is related to microglial activation.However,how Vav1 participates in the inflammato ry response after cerebral ischemia/reperfusion inj ury remains unclea r.In this study,we subjected rats to occlusion and repe rfusion of the middle cerebral artery and subjected the BV-2 mic roglia cell line to oxygen-glucose deprivatio n/reoxygenation to mimic cerebral ischemia/repe rfusion in vivo and in vitro,respectively.We found that Vav1 levels were increased in the brain tissue of rats subjected to occlusion and reperfusion of the middle cerebral arte ry and in BV-2 cells subjected to oxygen-glucose deprivation/reoxygenation.Silencing Vav1 reduced the cerebral infarct volume and brain water content,inhibited neuronal loss and apoptosis in the ischemic penumbra,and im p roved neurological function in rats subjected to occlusion and repe rfusion of the middle cerebral artery.Further analysis showed that Vav1 was almost exclusively localized to microglia and that Vav1 downregulation inhibited microglial activation and the NOD-like receptor pyrin 3(NLRP3) inflammasome in the ischemic penumbra,as well as the expression of inflammato ry facto rs.In addition,Vov1 knoc kdown decreased the inflammatory response exhibited by BV-2 cells after oxygen-glucose deprivation/reoxyge nation.Taken together,these findings show that silencing Vav1 attenuates inflammation and neuronal apoptosis in rats subjected to cerebral ischemia/repe rfusion through inhibiting the activation of mic roglia and NLRP3 inflammasome.展开更多
Urolithin A(UA)is a natural metabolite produced from polyphenolics in foods such as pomegranates,berries,and nuts.UA is neuroprotective against Parkinson’s disease,Alzheimer’s disease,and cerebral hemorrhage.However...Urolithin A(UA)is a natural metabolite produced from polyphenolics in foods such as pomegranates,berries,and nuts.UA is neuroprotective against Parkinson’s disease,Alzheimer’s disease,and cerebral hemorrhage.However,its effect against traumatic brain injury remains unknown.In this study,we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA.We found that UA greatly reduced brain edema;increased the expression of tight junction proteins in injured cortex;increased the immunopositivity of two neuronal autophagy markers,microtubule-associated protein 1A/B light chain 3A/B(LC3)and p62;downregulated protein kinase B(Akt)and mammalian target of rapamycin(mTOR),two regulators of the phosphatidylinositol 3-kinase(PI3K)/Akt/mTOR signaling pathway;decreased the phosphorylation levels of inhibitor of NFκB(IκB)kinase alpha(IKKα)and nuclear factor kappa B(NFκB),two regulators of the neuroinflammation-related Akt/IKK/NFκB signaling pathway;reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex;and improved mouse neurological function.These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury,and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NFκB signaling pathways,thus reducing neuroinflammation and enhancing autophagy.展开更多
Objective:Based on the BDNF/TrkB/CREB pathway,to explore the mechanism of neuronal apoptosis and brain developmental injury in the hippocampus of hypoxic-ischemic neonatal rats.Methods:Wistar young rats were ligated o...Objective:Based on the BDNF/TrkB/CREB pathway,to explore the mechanism of neuronal apoptosis and brain developmental injury in the hippocampus of hypoxic-ischemic neonatal rats.Methods:Wistar young rats were ligated on one side of the common carotid artery and placed in an 8%oxygen and 92%nitrogen hypoxia box for 2 h to prepare hypoxic-ischemic brain injury models.Healthy rats were used as the control group.Control group and model group were selected,with 10 rats in each group,and the learning and memory ability was tested by Y-maze;2,3,5-triphenyltetrazolium chloride(TTC)staining was used to detect brain tissue damage;Western blot was performed to determine the expression of brain-derived neurotrophic factor(BDNF),tyrosine protein kinase B(TrKB)and cAMP-response element binding protein(CREB)in hippocampal tissue.Another 15 mice in the control group and 60 mice in the model group were divided into negative control group(NC),BDNF overexpression group(LV-BDNF),TrkB overexpression group(LV-TrkB),and CREB overexpression group(LV-CREB),blank vector,BDNF,TrkB,CREB adenovirus overexpression vector was injected into the tail vein.Y-maze test for learning and memory ability;TTC staining method to detect brain tissue damage;neuronal apoptosis in the hippocampus were detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling;Western blot to detect the level of neuronal apoptosis in the hippocampus.Apoptosis-related protein B-cell lymphoma-2(Bcl-2),BCL2associated X protein(Bcl-2 Assaciated X,Bax)and nuclear factor kappaB(NFκB)expression.Results:The learning and memory ability of the young mice in the model group was significantly reduced,the brain infarct volume was significantly increased,the expressions of BDNF and TrkB proteins in the hippocampus were significantly increased,and the expression of CREB proteins was significantly decreased;After overexpression of BDNF and TrkB CREB,in the LVBDNF,LVTrkB,and LVCREB group,the learning and memory ability of young mice were significantly improved,the brain infarct volume were significantly reduced,the hippocampal neuronal apoptosis were significantly reduced,The protein expression of Bax and NFκB were significantly decreased and the protein expression of Bcl2 were significantly enhanced.Conclusion:The expression of BDNF/TrkB/CREB is abnormal in HIBI model young mice.Overexpression of BDNF/TrkB/CREB can improve the learning and memory ability of young mice,repair brain tissue damage,and inhibit neuronal apoptosis.Therefore,the mechanism of HIBI may be related to BDNF/TrkB/CREB pathways.展开更多
BACKGROUND: Aggregation of α-synuclein is the major component of Lewy bodies, which are the pathological hallmarks of Parkinson disease (PD). Although the mechanism of this protein aggregates is unclear, previous stu...BACKGROUND: Aggregation of α-synuclein is the major component of Lewy bodies, which are the pathological hallmarks of Parkinson disease (PD). Although the mechanism of this protein aggregates is unclear, previous study showed that environmental toxins such as rotenone could induce the expression and aggregation of α-synuclein. OBJECTIVE: To observe the role of α-synuclein in PD. DESIGN: A randomized controlled trial. SETTING: Beijing Institute for Neuroscience, Capital University of Medical Sciences. MATERIALS: This study was performed from July 2005 to January 2006 at the Beijing Institute for Neuroscience, Capital University of Medical Sciences. Human dopaminergic neuroblastoma SH-SY5Y cells were provided by Beijing Institute for Neuroscience, Capital University of Medical Sciences. METHODS: Human dopaminergic neuroblastoma SH-SY5Y cells were treated to make α-synuclein over express. Rotenone was added into the medium of cultured both native SH-SY5Y cells and α-synuclein-overexpression SH-SY5Y cells. Lactate dehydrogenase (LDH) assay was used to detect with the cell viability. Flow cytometry and electrophoresis were adopted to measure the cell apoptosis. MAIN OUTCOME MEASURES: Cell viability, DNA fragmentation, and the number of cell apoptosis. RESULTS: After being treated with rotenone, LDH activity of α-synuclein overexpressed SH-SY5Y cells was (76.625±6.34) μkat/L, which was significantly lower than that of control group (P < 0.05). As compared with normal SH-SY5Y cell, α-synuclein over-expressed SH-SY5Y cells had less DNA fragments and apoptotic cells. α-synuclein might play a role in cell apoptosis induced by rotenone, which was also confirmed by using of antioxidant reagent. CONCLUSION: α-synuclein may partially protect against cell apoptosis induced by rotenone in SH-SY5Y cells.展开更多
BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the stud...BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats. OBJECTIVE: To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury. DESIGN: Randomized grouping design, controlled animal trial.SETTING: Department of Anesthesiology, the Medical School Hospital of Qingdao University.MATERIALS: Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents: homemade beat machine, ketamine hydrochloride (Hengrui Pharmaceutical Factory, Jiangsu), rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit (Boster Co.,Ltd., Wuhan). METHODS: This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine (120 mg/kg) one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal morphology was observed. AQP-4 expression and neuronal apoptosis were measured with immunohistochemical method and TUNEL method respectively. MAIN OUTCOME MEASURES: Water content in brain tissue, neuronal morphology, the number of AQP-4 positive neurons and TUNEL positive neurons in rats of two groups at each time point after injury.RESULTS: Totally 150 rats entered the stage of result analysis. ① Water content of brain tissue: The water content of brain tissue at each time point after injury in the ketamine-treated group was lower than that in the control group. There were very significant differences in water content at 12 and 24 hours after injury respectively between ketamine-treated group and control group [(77.34±2.35)% vs.(82.31±1.48)%;(78.01±2.21)%vs.(83.86±2.37)%,t=4.001 6,4.036 7,both P < 0.01]. ② Neuronal morphology: Pathological changes in traumatic region and peripheral region of injury in the ketamine-treated group were significantly lessened, and necrotic and apoptotic cells in the ketamine-treated group were also significantly reduced as compared with control group. ③ AQP-4 expression: AQP-4 positive neurons at each time point in the ketamine-treated group were significantly less than those in the control group. There were very significant differences in AQP-4 expression at 12 and 24 hours after injury between ketamine-treated group and control group [(34.17±4.74) /visual field vs. (43.42±5.65) /visual field;(40.83±3.17) /visual field vs. (58.88±6.23) /visual field,t =3.966 3,8.165 7, both P < 0.01]. ④ Neuronal apoptosis: TUNEL positive neurons at each time point in the ketamine-treated group were less than those in the control group. There were very significant differences in the neuronal apoptosis at 12 and 24 hours after injury between ketamine-treated group and control group [(26.25±3.04) /visual field vs. (32.75±4.39) /visual field;(29.33±4.02) /visual field vs. (39.83±5.61) /visual field,t=3.849 3,5.169 2,both P < 0.01].CONCLUSION: Ketamine can reduce brain edema, AQP-4 expression and neuronal apoptosis following brain injury in rats, and has obvious therapeutic effect on brain injury, especially at 12 and 24 hours after injury.展开更多
Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke,but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported.A rat model of traumat...Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke,but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported.A rat model of traumatic brain injury was established by weight-drop method.The tissue plasminogen activator inhibitor neuroserpin(5μL,0.25 mg/mL)was injected into the lateral ventricle.Neurological function was assessed by neurological severity score.Neuronal and axonal injuries were assessed by hematoxylin-eosin staining and Bielschowsky silver staining.Protein level of endogenous tissue plasminogen activator was analyzed by western blot assay.Apoptotic marker cleaved caspase-3,neuronal marker neurofilament light chain,astrocyte marker glial fibrillary acidic protein and microglial marker Iba-1 were analyzed by immunohistochemical staining.Apoptotic cell types were detected by immunofluorescence double labeling.Apoptotic cells in the damaged cortex were detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling staining.Degenerating neurons in the damaged cortex were detected by Fluoro-Jade B staining.Expression of tissue plasminogen activator was increased at 6 hours,and peaked at 3 days after traumatic brain injury.Neuronal apoptosis and axonal injury were detected after traumatic brain injury.Moreover,neuroserpin enhanced neuronal apoptosis,neuronal injury and axonal injury,and activated microglia and astrocytes.Neuroserpin further deteriorated neurobehavioral function in rats with traumatic brain injury.Our findings confirm that inhibition of endogenous tissue plasminogen activator aggravates neuronal apoptosis and axonal injury after traumatic brain injury,and activates microglia and astrocytes.This study was approved by the Biomedical Ethics Committee of Animal Experiments of Shaanxi Province of China in June 2015.展开更多
Studies have confirmed a strong association between activation of the endoplasmic reticulum stress pathway and cerebral ischemia/reperfusion(I/R) injury.In this study,three key proteins in the endoplasmic reticulum st...Studies have confirmed a strong association between activation of the endoplasmic reticulum stress pathway and cerebral ischemia/reperfusion(I/R) injury.In this study,three key proteins in the endoplasmic reticulum stress pathway(glucose-regulated protein 78,caspase-12,and C/EBP homologous protein) were selected to examine the potential mechanism of endoplasmic reticulum stress in the neuroprotective effect of G protein-coupled estrogen receptor.Female Sprague-Dawley rats received ovariectomy(OVX),and then cerebral I/R rat models(OVX+ I/R) were established by middle cerebral artery occlusion.Immediately after I/R,rat models were injected with 100 μg/kg E2(OVX + I/R +E2),or 100 μg/kg G protein-coupled estrogen receptor agonist G1(OVX + I/R + G1) in the lateral ventricle.Longa scoring was used to detect neurobehavioral changes in each group.Infarct volumes were measured by 2,3,5-triphenyltetrazolium chloride staining.Morphological changes in neurons were observed by Nissl staining.Terminal dexynucleotidyl transferase-mediated nick end-labeling staining revealed that compared with the OVX + I/R group,neurological function was remarkably improved,infarct volume was reduced,number of normal Nissl bodies was dramatically increased,and number of apoptotic neurons in the hippocampus was decreased after E2 and G1 intervention.To detect the expression and distribution of endoplasmic reticulum stress-related proteins in the endoplasmic reticulum,caspase-12 distribution and expression were detected by immunofluorescence,and mRNA and protein levels of glucose-regulated protein 78,caspase-12,and C/EBP homologous protein were determined by polymerase chain reaction and western blot assay.The results showed that compared with the OVX+ I/R group,E2 and G1 treatment obviously decreased mRNA and protein expression levels of glucose-regulated protein 78,C/EBP homologous protein,and caspase-12.However,the G protein-coupled estrogen receptor antagonist G15(OVX + I/R + E2 + G15) could eliminate the effect of E2 on cerebral I/R injury.These results confirm that E2 and G protein-coupled estrogen receptor can inhibit the expression of endoplasmic reticulum stress-related proteins and neuronal apoptosis in the hippocampus,thereby improving dysfunction caused by cerebral I/R injury.Every experimental protocol was approved by the Institutional Ethics Review Board at the First Affiliated Hospital of Shihezi University School of Medicine,China(approval No.SHZ A2017-171) on February 27,2017.展开更多
RehabilNation training is believed to be beneficial to patients with stroke, but its molecular mechanism is still unclear. Rat models of cerebral ischemic stroke were established by middle cerebral artery occlusion/re...RehabilNation training is believed to be beneficial to patients with stroke, but its molecular mechanism is still unclear. Rat models of cerebral ischemic stroke were established by middle cerebral artery occlusion/reperfusion, and then received treadmill training of different intens让ies, twice a day for 30 minutes for 1 week. Low-intensity training was conducted at 5 m/min, with a 10-minute running, 10-minute rest, and 10-minute running cycle. In the moderate-intensity training, the intensity gradually increased from 5 m/min to 10 m/min in 5 minutes, with the same rest cycle as above. In high-intensity training, the intensity gradually increased from 5 m/min to 25 m/min in 5 minutes, with the same rest cycle as above. The Bederson scale was used to evaluate the improvement of motor function. Infarct volume was detected using 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining was applied to detect the apoptosis of nerve cells in brain tissue. Western blot assay was employed to analyze the activation of cyclic adenosine monophosphate (cAMP)/protein kinase A and Akt/glycogen synthase kinase-3卩 signaling pathways in rat brain tissue. All training intensities reduced the neurological deficit score, infarct volume, and apoptosis in nerve cells in brain tissue of stroke rats. Training intensities activated the cAMP/protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This activation was more obvious with higher training intensities. These changes were reversed by intracerebroventricular injection of protein kinase A inhibitor Rp-cAMP. Our findings indicate that the neuroprotective effect of rehabilitation training is achieved via activation of the cAMP/ protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This study was approved by the Ethics Committee of Animal Experimentation in Shanghai No. 8 Peoples Hospital, China.展开更多
Objective Cerebral ischemia/reperfusion(I/R)is a potential factor for lethal injury,and currently lacks effective remedies.Bauhinia championii extracts(BCEs)have been reported to exhibit anti-oxidative and anti-hypoxi...Objective Cerebral ischemia/reperfusion(I/R)is a potential factor for lethal injury,and currently lacks effective remedies.Bauhinia championii extracts(BCEs)have been reported to exhibit anti-oxidative and anti-hypoxia properties.The current work aimed to study whether BCE could alleviate neuronal injury caused by I/R.Methods To investigate the protective effects of BCE,oxygen-glucose deprivation/reperfusion(OGD/R)was applied to the HT22 cell line in vitro and to a cerebral I/R mouse model in vivo.Results Under OGD/R,the survival of HT22 cells was significantly prolonged after treatment with BCE.In vivo,BCE significantly reduced the infarct area and decreased neuronal apoptosis caused by I/R.It was further found that OGD/R could trigger endoplasmic reticulum(ER)stress and induce ER stress-mediated neuronal apoptosis in vivo and in vitro,while BCE could effectively alleviate ER stress and neuronal apoptosis.Conclusion These results suggested that BCE exhibits neuroprotective effects by reducing ER stress-mediated apoptosis after cerebral I/R injury.BCE may therefore be an effective therapeutic regimen against cerebral I/R damage.展开更多
Objective: To investigate the effect and significance of electroacupuncture (EA) on neuronal apoptosis and hindlimb motor and bladder functional improvement in rats with acute spinal cord injury (SCI). Methods: Sixty ...Objective: To investigate the effect and significance of electroacupuncture (EA) on neuronal apoptosis and hindlimb motor and bladder functional improvement in rats with acute spinal cord injury (SCI). Methods: Sixty healthy Sprague Dawley rats were randomly assigned to sham, model, EA, and EA control groups (n = 15 each). EA group rats received EA treatment at Zhibian and Shuidao acupoints seven times daily, whereas EA control group rats received EA at two points, 0.5 cm away from Zhibian and Shuidao, respectively. Histomorphological changes in spinal cord tissue were examined using hematoxylin-eosin staining. Neuronal apoptosis was detected by TUNEL assay. Bcl-2, Bax, and Bad protein levels were detected using immunohistochemistry. Additionally, hindlimb motor function, residual urine volume and maximum bladder capacity were measured. Results: HE staining revealed a morphologically and structurally intact spinal cord in the EA group, and the tissue contained scattered blood cells without edema. In the EA control group, there were small morphological defects in the spinal cord, and the tissue contained fewer blood cells with local edema. Compared with the EA control and model groups, Bax and Bad levels were significantly decreased in the EA group and Bcl-2 expression was increased (P < 0.05). After SCI, hindlimb function scores, residual urine volume, and maximum bladder capacity in rats of the EA group significantly differed from those of the EA control group (P < 0.05). Conclusion: EA may induce SCI-induced improvements in hindlimb motor and bladder functions by affecting neuronal apoptosis and relevant gene expression changes.展开更多
BACKGROUND: Rifampicin inhibits the formation of α-synuclein multimer and protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyritine (MPTP)-induced PC12 cell apoptosis.OBJECTIVE: To compare the effect of rifampici...BACKGROUND: Rifampicin inhibits the formation of α-synuclein multimer and protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyritine (MPTP)-induced PC12 cell apoptosis.OBJECTIVE: To compare the effect of rifampicin pre-and post-treatment on tyrosine hydroxylase and α-synuclein expression in substantia nigra pars compacta in a rat model of Parkinson’s disease.DESIGN,TIME AND SETTING: A randomized,controlled experiment was performed at the Experimental Animal Center of Sun Yat-sen University North Campus (China) from November 2006 to October 2008.MATERIALS: Rifampicin was purchased from MD,USA;rotenone was purchased from Sigma,USA;mouse anti-rat α-synuclein monoclonal antibody was purchased from B&D,USA;and rabbit anti-rat tyrosine hydroxylase monoclonal antibody was purchased from Chemicon,USA.METHODS: A total of 72 male,Sprague Dawley rats,aged 8 weeks,were randomly assigned to 5 groups: blank control (n = 12),rifampicin (n = 12),rotenone (n = 16),rifampicin pre-treatment (n = 16),and rifampicin post-treatment (n = 16).Parkinson’s disease model rats were established via a subcutaneous injection of rotenone (1.5 mg/kg per day) in the three treatment groups,once a day for 3 successive weeks.Rifampicin (30 mg/kg per day) was intragastrically administered in the rifampicin pre-treatment group 3 days prior to rotenone induction and in the rifampicin post-treatment group 7 days after rotenone induction.Rats were treated with a subcutaneous injection of 1 mL/kg per day sunflower oil in the blank control group and an intragastric injection of 30 mg/kg per day rifampicin in the rifampicin group,once a day for 3 successive weeks in total.MAIN OUTCOME MEASURES: Prior to treatment and in the end of the 3rd week after treatment,the rats were evaluated using the modified neurological severity score.The substantia nigra from the rats was extracted for hematoxylin-eosin staining.Western blot analysis was performed to determine tyrosine hydroxylase and α-synuclein expression.RESULTS: Hematoxylin-eosin staining revealed a significant reduction in the number of substantia nigral neurons in the rotenone group,in addition to neurodegradation,hypopigmentation,and pyknosis.In the rifampicin pre-treatment and post-treatment groups,the number of dopaminergic neurons was significantly increased compared with the rotenone group (P < 0.01),with slight neuronal damage.Compared with the rotenone group,substantia nigral tyrosine hydroxylase expres-sion was significantly increased in the rifampicin pre-treatment and post-treatment groups (P < 0.01),but α-synuclein expression and modified neurological severity scores were significantly decreased (P < 0.01).In addition,the effect of rifampicin in the pre-treatment group was superior to the post-treatment group.There was no significant difference in tyrosine hydroxylase and α-synuclein expression,or in the modified neurological severity scores,between the blank control and rifampicin groups (P > 0.05).CONCLUSION: Rifampicin significantly attenuated neuropathological and behavioral motor deficits induced by rotenone.Moreover,rifampicin enhanced tyrosine hydroxylase expression,but inhibited α-synuclein expression.The effect of rifampicin pre-treatment was superior to rifampicin post-treatment.展开更多
We have found that Batroxobin plays a protactive role in ischemic brain injury, which attracted us to investigate the effect of Batroxobin on apoptosis of neurons during cerebral ischemia and reperfusion. The apoptoti...We have found that Batroxobin plays a protactive role in ischemic brain injury, which attracted us to investigate the effect of Batroxobin on apoptosis of neurons during cerebral ischemia and reperfusion. The apoptotic cells in ischemic rat brains at different reperfusion intervals were tested with method of TdT-mediated dUTP-DIG nick end labeling (TUNEL) and the effect of Batroxobin on the apoptosis of neurons was studied in left middle cerebral artery (LMCA) occlusion and reperfusion in rat models (n=18). The results showed that few scattered apoptosis cells were observed in right cerebral hemispheres after LMCA occlusion and reperfusion, and that a lot of apoptosis cells were found in left ischemic cortex and caudoputamen at 12h reperfusion, and they reached peak at 24h^48h reperfusion. However, in the rats pretreated with Batroxobin, the number of apoptosis cells in left cerebral cortex and caudoputamen reduced significantly and the neuronal damage was much milder at 24h reperfusion than that of saline-treated rats. The results indicate that administration of Batroxobin may reduce the apoptosis of neurons induced by cerebral ischemia and reperfusion and afford significant cerebroprotection in the model of focal cerebral ischemia and reperfusion.展开更多
Objective:To investigate whether Hainan papayas has protective effects in an Aimary neuron injury model and elucidate the underlying molecular mecha β 40-induced prnism.Methods:Cultured primary neurons from the dorsa...Objective:To investigate whether Hainan papayas has protective effects in an Aimary neuron injury model and elucidate the underlying molecular mecha β 40-induced prnism.Methods:Cultured primary neurons from the dorsal root ganglia(DRG) of Sprague-Dawley(SD) rats were treated with 20 μM A culture medium β 40 peptide,100 μg/L Hainan papaya water extract,peptide plus extract,or for 24 h.Cell viability was measured by MTT assay,and neuronal apoptosis was evaluated by DAPI staining.ERK signaling pathway-associated molecule activation and changes in Bax expression were analyzed by Western blotting and immunofluorescence.Results:A cell viability rate of(44.11±6.59)% in the Ading different concentrations of the extract β 40 group was rescued to(79.13±6.64)% by ad.DAPI showed pyknotic nuclei in 39.5% of A β 40-treated cells;the fraction dropped to 17.4% in the 100 μg/L extract group.ERK phosphorylation was observed in the Aent with 100 μg/L extract.Hainan papaya water ex β 40 group but was ameliorated by pretreatmtract also prevented Ation of MEK,RSK1 and CREB associated with ERK signaling and d β 40-induced phosphorylaownregulated Bax expression in the neurons.Conclusion:The resultss suggest that Hainan papaya water extract has protective effects on neurons;the mechanism may be related to suppression of ERK signaling activation.展开更多
Studies have shown that downregulation of nuclear-enriched autosomal transcript 1(Neat1)may adversely affect the recovery of nerve function and the increased loss of hippocampal neurons in mice.Whether Neat1 has prote...Studies have shown that downregulation of nuclear-enriched autosomal transcript 1(Neat1)may adversely affect the recovery of nerve function and the increased loss of hippocampal neurons in mice.Whether Neat1 has protective or inhibitory effects on neuronal cell apoptosis after secondary brain injury remains unclear.Therefore,the effects of Neat1 on neuronal apoptosis were observed.C57 BL/6 primary neurons were obtained from the cortices of newborn mice and cultured in vitro,and an oxygen and glucose deprivation cell model was established to simulate the secondary brain injury that occurs after traumatic brain injury in vitro.The level of Neat1 expression in neuronal cells was regulated by constructing a recombinant adenovirus to infect neurons,and the effects of Neat1 expression on neuronal apoptosis after oxygen and glucose deprivation were observed.The experiment was divided into four groups:the control group,without any treatment,received normal culture;the oxygen and glucose deprivation group were subjected to the oxygen and glucose deprivation model protocol;the Neat1 overexpression and Neat1 downregulation groups were treated with Neat1 expression intervention techniques and were subjected to the in oxygen and glucose deprivation protocol.The protein expression levels of neurons p53-induced death domain protein 1(PIDD1,a pro-apoptotic protein),caspase-2(an apoptotic priming protein),cytochrome C(a pro-apoptotic protein),and cleaved caspase-3(an apoptotic executive protein)were measured in each group using the western blot assay.To observe changes in the intracellular distribution of cytochrome C,the expression levels of cytochrome C in the cytoplasm and mitochondria of neurons from each group were detected by western blot assay.Differences in the cell viability and apoptosis rate between groups were detected by cell-counting kit 8 assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay,respectively.The results showed that the apoptosis rate,PIDD1,caspase-2,and cleaved caspase-3 expression levels significantly decreased,and cell viability significantly improved in the Neat1 overexpression group compared with the oxygen and glucose deprivation group;however,Neat1 downregulation reversed these changes.Compared with the Neat1 downregulation group,the cytosolic cytochrome C level in the Neat1 overexpression group significantly decreased,and the mitochondrial cytochrome C level significantly increased.These data indicate that Neat1 upregulation can reduce the release of cytochrome C from the mitochondria to the cytoplasm by inhibiting the PIDD1-caspase-2 pathway,reducing the activation of caspase-3,and preventing neuronal apoptosis after oxygen and glucose deprivation,which might reduce secondary brain injury after traumatic brain injury.All experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Chongqing Medical University,China,on December 19,2020(approval No.2020-895).展开更多
To observe the effects of different acupuncture manipulations on blood pressure and target organ damage in spontaneously hypertensive rats(SHRs), this study used the reinforcing twirling method(1.5–2-mm depth; rotati...To observe the effects of different acupuncture manipulations on blood pressure and target organ damage in spontaneously hypertensive rats(SHRs), this study used the reinforcing twirling method(1.5–2-mm depth; rotating needle clockwise for 360° and then counter clockwise for 360°, with the thumb moving heavily forward and gently backward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), the reducing twirling method(1.5–2-mm depth; rotating needle counter clockwise for 360° and then clockwise for 360°, with the thumb moving heavily backward and gently forward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), and the needle retaining method(1.5–2-mm depth and retaining the needle for 10 minutes). Bilateral Taichong(LR3) was treated by acupuncture using different manipulations and manual stimulation. Reinforcing twirling, reducing twirling, and needle retaining resulted in a decreased number of apoptotic cells, reduced Bax m RNA and protein expression, and an increased Bcl-2/Bax ratio in the hippocampus compared with the SHR group. Among these groups, the Bcl-2/Bax protein ratio was highest in the reducing twirling group, and the Bcl-2/Bax m RNA ratio was highest in the needle retaining group. These results suggest that reinforcing twirling, reducing twirling, and needle retaining methods all improve blood pressure and prevent target organ damage by increasing the hippocampal Bcl-2/Bax ratio and inhibiting cell apoptosis in the hippocampus in SHR.展开更多
Several studies have suggested that exogenous glial cell line-derived neurotrophic factor may pro-tect neurons from cerebral ischemic injury. However, the mechanisms underlying the neuroprotec-tive effects of endogeno...Several studies have suggested that exogenous glial cell line-derived neurotrophic factor may pro-tect neurons from cerebral ischemic injury. However, the mechanisms underlying the neuroprotec-tive effects of endogenous glial cell line-derived neurotrophic factor remain unclear. The present experiments sought to elucidate the influence of various conditioned media on neuronal apoptosis, using a normal culture medium for astrocytes, an astrocyte medium highly expressing glial cell line-derived neurotrophic factor, and an astrocyte medium in which glial cell line-derived neurotro-phic factor expression was silenced using RNAi technology. The results confirmed that the use of RNAi silencing to target pretreated glial cell line-derived neurotrophic factor expression promoted neuronal apoptosis. In addition, oxygen and glucose deprivation preconditioning was found to upregulate glial cell line-derived neurotrophic factor expression, and significantly reduce neuronal apoptosis.展开更多
This study investigated the neuroprotective effect of Yiqi Bushen prescription (YQBS, supplementing qi and tonifying kidney) on neuronal cell apoptosis. Following YQBS treatment, the number of surviving hippocampal ne...This study investigated the neuroprotective effect of Yiqi Bushen prescription (YQBS, supplementing qi and tonifying kidney) on neuronal cell apoptosis. Following YQBS treatment, the number of surviving hippocampal neurons increased, anti-apoptotic Bcl-2 expression increased and pro-apoptotic Bax expression decreased. In addition, diabetic rats exhibited improved learning and memory. YQBS treatment also increased Bcl-2 mRNA expression and the ratio of Bcl-2/Bax, but decreased levels of hypoxia-inducible factor-1α mRNA and Bax mRNA expression after high-glucose/hypoxia-induced injury. Results demonstrated that YQBS inhibited hippocampal neuronal apoptosis by decreasing hypoxia-inducible factor-1α expression and increasing Bcl-2 expression, thereby improving cognitive impairment in diabetic rats.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81971870,82172173(both to MCL)。
文摘Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.
基金supported by the National Natural Science Foundation of China,No.81772452(to NL)the Fujian Province Joint Funds for the Innovation of Science and Technology,No.2020Y9065(to NL)+1 种基金Fujian Province Special Foundation for Natural Science Innovation Project,No.2016B014(to NL)the Natural Science Foundation of Fujian Province,No.2019J01160(to XHJ).
文摘Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia.However,whether there is a synergistic effect between the two remains unclear.In this study,we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours.Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes(MSC-exos)via the tail vein and underwent 14 successive days of treadmill exercise.Neurological assessment,histopathology,and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume,evident synaptic formation and axonal regeneration,and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment.These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone.Mechanistically,further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling.These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment,which may be related to activation of the JNK1/c-Jun signaling pathway.This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.
基金supported by the Natural Science Foundation of Liaoning Province,No.2021-MS-061(to LZhang)。
文摘Circular RNAs can regulate the development and progression of ischemic cerebral disease.However,it remains unclear whether they play a role in acute ischemic stroke.To investigate the role of the circular RNA Rap1b(circRap1b)in acute ischemic stroke,in this study we established an in vitro model of acute ischemia and hypoxia by subjecting HT22 cells to oxygen and glucose deprivation and a mouse model of acute ischemia and hypoxia by occluding the right carotid artery.We found that circRap1b expression was remarkably down-regulated in the hippocampal tissue of the mouse model and in the HT22 cell model.In addition,Hoxa5 expression was strongly up-regulated in response to circRap1b overexpression.Hoxa5 expression was low in the hippocampus of a mouse model of acute ischemia and in HT22-AIS cells,and inhibited HT22-AIS cell apoptosis.Importantly,we found that circRap1b promoted Hoxa5 transcription by recruiting the acetyltransferase Kat7 to induce H3K14ac modification in the Hoxa5 promoter region.Hoxa5 regulated neuronal apoptosis by activating transcription of Fam3a,a neuronal apoptosis-related protein.These results suggest that circRap1b regulates Hoxa5 transcription and expression,and subsequently Fam3a expression,ultimately inhibiting cell apoptosis.Lastly,we explored the potential clinical relevance of circRap1b and Hoxa5 in vivo.Taken together,these findings demonstrate the mechanism by which circRap1b inhibits neuronal apoptosis in acute ischemic stroke.
基金Natural Science Foundation of Liaoning Province (General Program),No.2017010825 (to JQ)。
文摘Microglia,which are the resident macrophages of the central nervous system,are an important part of the inflammatory response that occurs after cerebral ischemia.Vav guanine nucleotide exchange factor 1(Vav1) is a guanine nucleotide exchange factor that is related to microglial activation.However,how Vav1 participates in the inflammato ry response after cerebral ischemia/reperfusion inj ury remains unclea r.In this study,we subjected rats to occlusion and repe rfusion of the middle cerebral artery and subjected the BV-2 mic roglia cell line to oxygen-glucose deprivatio n/reoxygenation to mimic cerebral ischemia/repe rfusion in vivo and in vitro,respectively.We found that Vav1 levels were increased in the brain tissue of rats subjected to occlusion and reperfusion of the middle cerebral arte ry and in BV-2 cells subjected to oxygen-glucose deprivation/reoxygenation.Silencing Vav1 reduced the cerebral infarct volume and brain water content,inhibited neuronal loss and apoptosis in the ischemic penumbra,and im p roved neurological function in rats subjected to occlusion and repe rfusion of the middle cerebral artery.Further analysis showed that Vav1 was almost exclusively localized to microglia and that Vav1 downregulation inhibited microglial activation and the NOD-like receptor pyrin 3(NLRP3) inflammasome in the ischemic penumbra,as well as the expression of inflammato ry facto rs.In addition,Vov1 knoc kdown decreased the inflammatory response exhibited by BV-2 cells after oxygen-glucose deprivation/reoxyge nation.Taken together,these findings show that silencing Vav1 attenuates inflammation and neuronal apoptosis in rats subjected to cerebral ischemia/repe rfusion through inhibiting the activation of mic roglia and NLRP3 inflammasome.
基金supported by the National Natural Science Foundation of China,Nos.81974189(to HLT),81801236(to QYG and LC),82001310(to DXY).
文摘Urolithin A(UA)is a natural metabolite produced from polyphenolics in foods such as pomegranates,berries,and nuts.UA is neuroprotective against Parkinson’s disease,Alzheimer’s disease,and cerebral hemorrhage.However,its effect against traumatic brain injury remains unknown.In this study,we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA.We found that UA greatly reduced brain edema;increased the expression of tight junction proteins in injured cortex;increased the immunopositivity of two neuronal autophagy markers,microtubule-associated protein 1A/B light chain 3A/B(LC3)and p62;downregulated protein kinase B(Akt)and mammalian target of rapamycin(mTOR),two regulators of the phosphatidylinositol 3-kinase(PI3K)/Akt/mTOR signaling pathway;decreased the phosphorylation levels of inhibitor of NFκB(IκB)kinase alpha(IKKα)and nuclear factor kappa B(NFκB),two regulators of the neuroinflammation-related Akt/IKK/NFκB signaling pathway;reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex;and improved mouse neurological function.These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury,and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NFκB signaling pathways,thus reducing neuroinflammation and enhancing autophagy.
基金Hainan Provincial Natural Science Foundation of China(NO.819QN388)。
文摘Objective:Based on the BDNF/TrkB/CREB pathway,to explore the mechanism of neuronal apoptosis and brain developmental injury in the hippocampus of hypoxic-ischemic neonatal rats.Methods:Wistar young rats were ligated on one side of the common carotid artery and placed in an 8%oxygen and 92%nitrogen hypoxia box for 2 h to prepare hypoxic-ischemic brain injury models.Healthy rats were used as the control group.Control group and model group were selected,with 10 rats in each group,and the learning and memory ability was tested by Y-maze;2,3,5-triphenyltetrazolium chloride(TTC)staining was used to detect brain tissue damage;Western blot was performed to determine the expression of brain-derived neurotrophic factor(BDNF),tyrosine protein kinase B(TrKB)and cAMP-response element binding protein(CREB)in hippocampal tissue.Another 15 mice in the control group and 60 mice in the model group were divided into negative control group(NC),BDNF overexpression group(LV-BDNF),TrkB overexpression group(LV-TrkB),and CREB overexpression group(LV-CREB),blank vector,BDNF,TrkB,CREB adenovirus overexpression vector was injected into the tail vein.Y-maze test for learning and memory ability;TTC staining method to detect brain tissue damage;neuronal apoptosis in the hippocampus were detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling;Western blot to detect the level of neuronal apoptosis in the hippocampus.Apoptosis-related protein B-cell lymphoma-2(Bcl-2),BCL2associated X protein(Bcl-2 Assaciated X,Bax)and nuclear factor kappaB(NFκB)expression.Results:The learning and memory ability of the young mice in the model group was significantly reduced,the brain infarct volume was significantly increased,the expressions of BDNF and TrkB proteins in the hippocampus were significantly increased,and the expression of CREB proteins was significantly decreased;After overexpression of BDNF and TrkB CREB,in the LVBDNF,LVTrkB,and LVCREB group,the learning and memory ability of young mice were significantly improved,the brain infarct volume were significantly reduced,the hippocampal neuronal apoptosis were significantly reduced,The protein expression of Bax and NFκB were significantly decreased and the protein expression of Bcl2 were significantly enhanced.Conclusion:The expression of BDNF/TrkB/CREB is abnormal in HIBI model young mice.Overexpression of BDNF/TrkB/CREB can improve the learning and memory ability of young mice,repair brain tissue damage,and inhibit neuronal apoptosis.Therefore,the mechanism of HIBI may be related to BDNF/TrkB/CREB pathways.
基金Special Funds for Major State Basic Research Program of China (973 Program), 2006CB500706Scientific Research Common Program of Beijing Municipal Commission of Education, No. KM200610025002
文摘BACKGROUND: Aggregation of α-synuclein is the major component of Lewy bodies, which are the pathological hallmarks of Parkinson disease (PD). Although the mechanism of this protein aggregates is unclear, previous study showed that environmental toxins such as rotenone could induce the expression and aggregation of α-synuclein. OBJECTIVE: To observe the role of α-synuclein in PD. DESIGN: A randomized controlled trial. SETTING: Beijing Institute for Neuroscience, Capital University of Medical Sciences. MATERIALS: This study was performed from July 2005 to January 2006 at the Beijing Institute for Neuroscience, Capital University of Medical Sciences. Human dopaminergic neuroblastoma SH-SY5Y cells were provided by Beijing Institute for Neuroscience, Capital University of Medical Sciences. METHODS: Human dopaminergic neuroblastoma SH-SY5Y cells were treated to make α-synuclein over express. Rotenone was added into the medium of cultured both native SH-SY5Y cells and α-synuclein-overexpression SH-SY5Y cells. Lactate dehydrogenase (LDH) assay was used to detect with the cell viability. Flow cytometry and electrophoresis were adopted to measure the cell apoptosis. MAIN OUTCOME MEASURES: Cell viability, DNA fragmentation, and the number of cell apoptosis. RESULTS: After being treated with rotenone, LDH activity of α-synuclein overexpressed SH-SY5Y cells was (76.625±6.34) μkat/L, which was significantly lower than that of control group (P < 0.05). As compared with normal SH-SY5Y cell, α-synuclein over-expressed SH-SY5Y cells had less DNA fragments and apoptotic cells. α-synuclein might play a role in cell apoptosis induced by rotenone, which was also confirmed by using of antioxidant reagent. CONCLUSION: α-synuclein may partially protect against cell apoptosis induced by rotenone in SH-SY5Y cells.
基金the Topic of Science and Technology Department of Qingdao City, No.2005kzd-22
文摘BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats. OBJECTIVE: To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury. DESIGN: Randomized grouping design, controlled animal trial.SETTING: Department of Anesthesiology, the Medical School Hospital of Qingdao University.MATERIALS: Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents: homemade beat machine, ketamine hydrochloride (Hengrui Pharmaceutical Factory, Jiangsu), rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit (Boster Co.,Ltd., Wuhan). METHODS: This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine (120 mg/kg) one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal morphology was observed. AQP-4 expression and neuronal apoptosis were measured with immunohistochemical method and TUNEL method respectively. MAIN OUTCOME MEASURES: Water content in brain tissue, neuronal morphology, the number of AQP-4 positive neurons and TUNEL positive neurons in rats of two groups at each time point after injury.RESULTS: Totally 150 rats entered the stage of result analysis. ① Water content of brain tissue: The water content of brain tissue at each time point after injury in the ketamine-treated group was lower than that in the control group. There were very significant differences in water content at 12 and 24 hours after injury respectively between ketamine-treated group and control group [(77.34±2.35)% vs.(82.31±1.48)%;(78.01±2.21)%vs.(83.86±2.37)%,t=4.001 6,4.036 7,both P < 0.01]. ② Neuronal morphology: Pathological changes in traumatic region and peripheral region of injury in the ketamine-treated group were significantly lessened, and necrotic and apoptotic cells in the ketamine-treated group were also significantly reduced as compared with control group. ③ AQP-4 expression: AQP-4 positive neurons at each time point in the ketamine-treated group were significantly less than those in the control group. There were very significant differences in AQP-4 expression at 12 and 24 hours after injury between ketamine-treated group and control group [(34.17±4.74) /visual field vs. (43.42±5.65) /visual field;(40.83±3.17) /visual field vs. (58.88±6.23) /visual field,t =3.966 3,8.165 7, both P < 0.01]. ④ Neuronal apoptosis: TUNEL positive neurons at each time point in the ketamine-treated group were less than those in the control group. There were very significant differences in the neuronal apoptosis at 12 and 24 hours after injury between ketamine-treated group and control group [(26.25±3.04) /visual field vs. (32.75±4.39) /visual field;(29.33±4.02) /visual field vs. (39.83±5.61) /visual field,t=3.849 3,5.169 2,both P < 0.01].CONCLUSION: Ketamine can reduce brain edema, AQP-4 expression and neuronal apoptosis following brain injury in rats, and has obvious therapeutic effect on brain injury, especially at 12 and 24 hours after injury.
文摘Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke,but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported.A rat model of traumatic brain injury was established by weight-drop method.The tissue plasminogen activator inhibitor neuroserpin(5μL,0.25 mg/mL)was injected into the lateral ventricle.Neurological function was assessed by neurological severity score.Neuronal and axonal injuries were assessed by hematoxylin-eosin staining and Bielschowsky silver staining.Protein level of endogenous tissue plasminogen activator was analyzed by western blot assay.Apoptotic marker cleaved caspase-3,neuronal marker neurofilament light chain,astrocyte marker glial fibrillary acidic protein and microglial marker Iba-1 were analyzed by immunohistochemical staining.Apoptotic cell types were detected by immunofluorescence double labeling.Apoptotic cells in the damaged cortex were detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling staining.Degenerating neurons in the damaged cortex were detected by Fluoro-Jade B staining.Expression of tissue plasminogen activator was increased at 6 hours,and peaked at 3 days after traumatic brain injury.Neuronal apoptosis and axonal injury were detected after traumatic brain injury.Moreover,neuroserpin enhanced neuronal apoptosis,neuronal injury and axonal injury,and activated microglia and astrocytes.Neuroserpin further deteriorated neurobehavioral function in rats with traumatic brain injury.Our findings confirm that inhibition of endogenous tissue plasminogen activator aggravates neuronal apoptosis and axonal injury after traumatic brain injury,and activates microglia and astrocytes.This study was approved by the Biomedical Ethics Committee of Animal Experiments of Shaanxi Province of China in June 2015.
基金supported by the National Natural Science Foundation of China,No.81560175,81260159(both to LL)
文摘Studies have confirmed a strong association between activation of the endoplasmic reticulum stress pathway and cerebral ischemia/reperfusion(I/R) injury.In this study,three key proteins in the endoplasmic reticulum stress pathway(glucose-regulated protein 78,caspase-12,and C/EBP homologous protein) were selected to examine the potential mechanism of endoplasmic reticulum stress in the neuroprotective effect of G protein-coupled estrogen receptor.Female Sprague-Dawley rats received ovariectomy(OVX),and then cerebral I/R rat models(OVX+ I/R) were established by middle cerebral artery occlusion.Immediately after I/R,rat models were injected with 100 μg/kg E2(OVX + I/R +E2),or 100 μg/kg G protein-coupled estrogen receptor agonist G1(OVX + I/R + G1) in the lateral ventricle.Longa scoring was used to detect neurobehavioral changes in each group.Infarct volumes were measured by 2,3,5-triphenyltetrazolium chloride staining.Morphological changes in neurons were observed by Nissl staining.Terminal dexynucleotidyl transferase-mediated nick end-labeling staining revealed that compared with the OVX + I/R group,neurological function was remarkably improved,infarct volume was reduced,number of normal Nissl bodies was dramatically increased,and number of apoptotic neurons in the hippocampus was decreased after E2 and G1 intervention.To detect the expression and distribution of endoplasmic reticulum stress-related proteins in the endoplasmic reticulum,caspase-12 distribution and expression were detected by immunofluorescence,and mRNA and protein levels of glucose-regulated protein 78,caspase-12,and C/EBP homologous protein were determined by polymerase chain reaction and western blot assay.The results showed that compared with the OVX+ I/R group,E2 and G1 treatment obviously decreased mRNA and protein expression levels of glucose-regulated protein 78,C/EBP homologous protein,and caspase-12.However,the G protein-coupled estrogen receptor antagonist G15(OVX + I/R + E2 + G15) could eliminate the effect of E2 on cerebral I/R injury.These results confirm that E2 and G protein-coupled estrogen receptor can inhibit the expression of endoplasmic reticulum stress-related proteins and neuronal apoptosis in the hippocampus,thereby improving dysfunction caused by cerebral I/R injury.Every experimental protocol was approved by the Institutional Ethics Review Board at the First Affiliated Hospital of Shihezi University School of Medicine,China(approval No.SHZ A2017-171) on February 27,2017.
基金supported by Clinical Study on Treatment of Cerebral Small Blood Vessel Disease by Integrated Traditional Chinese and Western Medicine,No.ZHYY-ZXYJHZX-201625
文摘RehabilNation training is believed to be beneficial to patients with stroke, but its molecular mechanism is still unclear. Rat models of cerebral ischemic stroke were established by middle cerebral artery occlusion/reperfusion, and then received treadmill training of different intens让ies, twice a day for 30 minutes for 1 week. Low-intensity training was conducted at 5 m/min, with a 10-minute running, 10-minute rest, and 10-minute running cycle. In the moderate-intensity training, the intensity gradually increased from 5 m/min to 10 m/min in 5 minutes, with the same rest cycle as above. In high-intensity training, the intensity gradually increased from 5 m/min to 25 m/min in 5 minutes, with the same rest cycle as above. The Bederson scale was used to evaluate the improvement of motor function. Infarct volume was detected using 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining was applied to detect the apoptosis of nerve cells in brain tissue. Western blot assay was employed to analyze the activation of cyclic adenosine monophosphate (cAMP)/protein kinase A and Akt/glycogen synthase kinase-3卩 signaling pathways in rat brain tissue. All training intensities reduced the neurological deficit score, infarct volume, and apoptosis in nerve cells in brain tissue of stroke rats. Training intensities activated the cAMP/protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This activation was more obvious with higher training intensities. These changes were reversed by intracerebroventricular injection of protein kinase A inhibitor Rp-cAMP. Our findings indicate that the neuroprotective effect of rehabilitation training is achieved via activation of the cAMP/ protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This study was approved by the Ethics Committee of Animal Experimentation in Shanghai No. 8 Peoples Hospital, China.
基金Health Commission of Hubei Province(No.ZY2021M014)the National Natural Science Foundation of China(No.81873725)+2 种基金Basic Scientific Research Funds of Department of Education of Zhejiang Province(No.KYYB202007)Zhejiang Basic Public Welfare Research Program(No.LGF22H280016)the“13th Five-Year”Chinese Medicine Key Discipline in Zhejiang Province-Chinese Medicine Quality and Functional Evaluation(No.2017-XK-A43).
文摘Objective Cerebral ischemia/reperfusion(I/R)is a potential factor for lethal injury,and currently lacks effective remedies.Bauhinia championii extracts(BCEs)have been reported to exhibit anti-oxidative and anti-hypoxia properties.The current work aimed to study whether BCE could alleviate neuronal injury caused by I/R.Methods To investigate the protective effects of BCE,oxygen-glucose deprivation/reperfusion(OGD/R)was applied to the HT22 cell line in vitro and to a cerebral I/R mouse model in vivo.Results Under OGD/R,the survival of HT22 cells was significantly prolonged after treatment with BCE.In vivo,BCE significantly reduced the infarct area and decreased neuronal apoptosis caused by I/R.It was further found that OGD/R could trigger endoplasmic reticulum(ER)stress and induce ER stress-mediated neuronal apoptosis in vivo and in vitro,while BCE could effectively alleviate ER stress and neuronal apoptosis.Conclusion These results suggested that BCE exhibits neuroprotective effects by reducing ER stress-mediated apoptosis after cerebral I/R injury.BCE may therefore be an effective therapeutic regimen against cerebral I/R damage.
文摘Objective: To investigate the effect and significance of electroacupuncture (EA) on neuronal apoptosis and hindlimb motor and bladder functional improvement in rats with acute spinal cord injury (SCI). Methods: Sixty healthy Sprague Dawley rats were randomly assigned to sham, model, EA, and EA control groups (n = 15 each). EA group rats received EA treatment at Zhibian and Shuidao acupoints seven times daily, whereas EA control group rats received EA at two points, 0.5 cm away from Zhibian and Shuidao, respectively. Histomorphological changes in spinal cord tissue were examined using hematoxylin-eosin staining. Neuronal apoptosis was detected by TUNEL assay. Bcl-2, Bax, and Bad protein levels were detected using immunohistochemistry. Additionally, hindlimb motor function, residual urine volume and maximum bladder capacity were measured. Results: HE staining revealed a morphologically and structurally intact spinal cord in the EA group, and the tissue contained scattered blood cells without edema. In the EA control group, there were small morphological defects in the spinal cord, and the tissue contained fewer blood cells with local edema. Compared with the EA control and model groups, Bax and Bad levels were significantly decreased in the EA group and Bcl-2 expression was increased (P < 0.05). After SCI, hindlimb function scores, residual urine volume, and maximum bladder capacity in rats of the EA group significantly differed from those of the EA control group (P < 0.05). Conclusion: EA may induce SCI-induced improvements in hindlimb motor and bladder functions by affecting neuronal apoptosis and relevant gene expression changes.
基金the Natural Science Foundation of Guangdong Province,No.04009355Science and Technology Planning Project of Guandong Province,China,05B33801003
文摘BACKGROUND: Rifampicin inhibits the formation of α-synuclein multimer and protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyritine (MPTP)-induced PC12 cell apoptosis.OBJECTIVE: To compare the effect of rifampicin pre-and post-treatment on tyrosine hydroxylase and α-synuclein expression in substantia nigra pars compacta in a rat model of Parkinson’s disease.DESIGN,TIME AND SETTING: A randomized,controlled experiment was performed at the Experimental Animal Center of Sun Yat-sen University North Campus (China) from November 2006 to October 2008.MATERIALS: Rifampicin was purchased from MD,USA;rotenone was purchased from Sigma,USA;mouse anti-rat α-synuclein monoclonal antibody was purchased from B&D,USA;and rabbit anti-rat tyrosine hydroxylase monoclonal antibody was purchased from Chemicon,USA.METHODS: A total of 72 male,Sprague Dawley rats,aged 8 weeks,were randomly assigned to 5 groups: blank control (n = 12),rifampicin (n = 12),rotenone (n = 16),rifampicin pre-treatment (n = 16),and rifampicin post-treatment (n = 16).Parkinson’s disease model rats were established via a subcutaneous injection of rotenone (1.5 mg/kg per day) in the three treatment groups,once a day for 3 successive weeks.Rifampicin (30 mg/kg per day) was intragastrically administered in the rifampicin pre-treatment group 3 days prior to rotenone induction and in the rifampicin post-treatment group 7 days after rotenone induction.Rats were treated with a subcutaneous injection of 1 mL/kg per day sunflower oil in the blank control group and an intragastric injection of 30 mg/kg per day rifampicin in the rifampicin group,once a day for 3 successive weeks in total.MAIN OUTCOME MEASURES: Prior to treatment and in the end of the 3rd week after treatment,the rats were evaluated using the modified neurological severity score.The substantia nigra from the rats was extracted for hematoxylin-eosin staining.Western blot analysis was performed to determine tyrosine hydroxylase and α-synuclein expression.RESULTS: Hematoxylin-eosin staining revealed a significant reduction in the number of substantia nigral neurons in the rotenone group,in addition to neurodegradation,hypopigmentation,and pyknosis.In the rifampicin pre-treatment and post-treatment groups,the number of dopaminergic neurons was significantly increased compared with the rotenone group (P < 0.01),with slight neuronal damage.Compared with the rotenone group,substantia nigral tyrosine hydroxylase expres-sion was significantly increased in the rifampicin pre-treatment and post-treatment groups (P < 0.01),but α-synuclein expression and modified neurological severity scores were significantly decreased (P < 0.01).In addition,the effect of rifampicin in the pre-treatment group was superior to the post-treatment group.There was no significant difference in tyrosine hydroxylase and α-synuclein expression,or in the modified neurological severity scores,between the blank control and rifampicin groups (P > 0.05).CONCLUSION: Rifampicin significantly attenuated neuropathological and behavioral motor deficits induced by rotenone.Moreover,rifampicin enhanced tyrosine hydroxylase expression,but inhibited α-synuclein expression.The effect of rifampicin pre-treatment was superior to rifampicin post-treatment.
文摘We have found that Batroxobin plays a protactive role in ischemic brain injury, which attracted us to investigate the effect of Batroxobin on apoptosis of neurons during cerebral ischemia and reperfusion. The apoptotic cells in ischemic rat brains at different reperfusion intervals were tested with method of TdT-mediated dUTP-DIG nick end labeling (TUNEL) and the effect of Batroxobin on the apoptosis of neurons was studied in left middle cerebral artery (LMCA) occlusion and reperfusion in rat models (n=18). The results showed that few scattered apoptosis cells were observed in right cerebral hemispheres after LMCA occlusion and reperfusion, and that a lot of apoptosis cells were found in left ischemic cortex and caudoputamen at 12h reperfusion, and they reached peak at 24h^48h reperfusion. However, in the rats pretreated with Batroxobin, the number of apoptosis cells in left cerebral cortex and caudoputamen reduced significantly and the neuronal damage was much milder at 24h reperfusion than that of saline-treated rats. The results indicate that administration of Batroxobin may reduce the apoptosis of neurons induced by cerebral ischemia and reperfusion and afford significant cerebroprotection in the model of focal cerebral ischemia and reperfusion.
基金supported by grants from the Science & Technology Department of Hainan Province,China (KJHZ2013-19)by grants from the Key Science and Technology Program of Hainan Province (ZDXM20120050)by the National Natural Science Foundation of China (81100246)
文摘Objective:To investigate whether Hainan papayas has protective effects in an Aimary neuron injury model and elucidate the underlying molecular mecha β 40-induced prnism.Methods:Cultured primary neurons from the dorsal root ganglia(DRG) of Sprague-Dawley(SD) rats were treated with 20 μM A culture medium β 40 peptide,100 μg/L Hainan papaya water extract,peptide plus extract,or for 24 h.Cell viability was measured by MTT assay,and neuronal apoptosis was evaluated by DAPI staining.ERK signaling pathway-associated molecule activation and changes in Bax expression were analyzed by Western blotting and immunofluorescence.Results:A cell viability rate of(44.11±6.59)% in the Ading different concentrations of the extract β 40 group was rescued to(79.13±6.64)% by ad.DAPI showed pyknotic nuclei in 39.5% of A β 40-treated cells;the fraction dropped to 17.4% in the 100 μg/L extract group.ERK phosphorylation was observed in the Aent with 100 μg/L extract.Hainan papaya water ex β 40 group but was ameliorated by pretreatmtract also prevented Ation of MEK,RSK1 and CREB associated with ERK signaling and d β 40-induced phosphorylaownregulated Bax expression in the neurons.Conclusion:The resultss suggest that Hainan papaya water extract has protective effects on neurons;the mechanism may be related to suppression of ERK signaling activation.
基金supported by the Youth Scienceof the National Natural Science Foundation of China,No.81701226(to LJ)。
文摘Studies have shown that downregulation of nuclear-enriched autosomal transcript 1(Neat1)may adversely affect the recovery of nerve function and the increased loss of hippocampal neurons in mice.Whether Neat1 has protective or inhibitory effects on neuronal cell apoptosis after secondary brain injury remains unclear.Therefore,the effects of Neat1 on neuronal apoptosis were observed.C57 BL/6 primary neurons were obtained from the cortices of newborn mice and cultured in vitro,and an oxygen and glucose deprivation cell model was established to simulate the secondary brain injury that occurs after traumatic brain injury in vitro.The level of Neat1 expression in neuronal cells was regulated by constructing a recombinant adenovirus to infect neurons,and the effects of Neat1 expression on neuronal apoptosis after oxygen and glucose deprivation were observed.The experiment was divided into four groups:the control group,without any treatment,received normal culture;the oxygen and glucose deprivation group were subjected to the oxygen and glucose deprivation model protocol;the Neat1 overexpression and Neat1 downregulation groups were treated with Neat1 expression intervention techniques and were subjected to the in oxygen and glucose deprivation protocol.The protein expression levels of neurons p53-induced death domain protein 1(PIDD1,a pro-apoptotic protein),caspase-2(an apoptotic priming protein),cytochrome C(a pro-apoptotic protein),and cleaved caspase-3(an apoptotic executive protein)were measured in each group using the western blot assay.To observe changes in the intracellular distribution of cytochrome C,the expression levels of cytochrome C in the cytoplasm and mitochondria of neurons from each group were detected by western blot assay.Differences in the cell viability and apoptosis rate between groups were detected by cell-counting kit 8 assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay,respectively.The results showed that the apoptosis rate,PIDD1,caspase-2,and cleaved caspase-3 expression levels significantly decreased,and cell viability significantly improved in the Neat1 overexpression group compared with the oxygen and glucose deprivation group;however,Neat1 downregulation reversed these changes.Compared with the Neat1 downregulation group,the cytosolic cytochrome C level in the Neat1 overexpression group significantly decreased,and the mitochondrial cytochrome C level significantly increased.These data indicate that Neat1 upregulation can reduce the release of cytochrome C from the mitochondria to the cytoplasm by inhibiting the PIDD1-caspase-2 pathway,reducing the activation of caspase-3,and preventing neuronal apoptosis after oxygen and glucose deprivation,which might reduce secondary brain injury after traumatic brain injury.All experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Chongqing Medical University,China,on December 19,2020(approval No.2020-895).
基金supported by the National Natural Science Foundation of China,No.81072861,81373727
文摘To observe the effects of different acupuncture manipulations on blood pressure and target organ damage in spontaneously hypertensive rats(SHRs), this study used the reinforcing twirling method(1.5–2-mm depth; rotating needle clockwise for 360° and then counter clockwise for 360°, with the thumb moving heavily forward and gently backward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), the reducing twirling method(1.5–2-mm depth; rotating needle counter clockwise for 360° and then clockwise for 360°, with the thumb moving heavily backward and gently forward, 60 times per minute for 1 minute, and retaining needle for 9 minutes), and the needle retaining method(1.5–2-mm depth and retaining the needle for 10 minutes). Bilateral Taichong(LR3) was treated by acupuncture using different manipulations and manual stimulation. Reinforcing twirling, reducing twirling, and needle retaining resulted in a decreased number of apoptotic cells, reduced Bax m RNA and protein expression, and an increased Bcl-2/Bax ratio in the hippocampus compared with the SHR group. Among these groups, the Bcl-2/Bax protein ratio was highest in the reducing twirling group, and the Bcl-2/Bax m RNA ratio was highest in the needle retaining group. These results suggest that reinforcing twirling, reducing twirling, and needle retaining methods all improve blood pressure and prevent target organ damage by increasing the hippocampal Bcl-2/Bax ratio and inhibiting cell apoptosis in the hippocampus in SHR.
基金Specialized Research Fund for the Doc-toral Program of Higher Education, No. 20060183053
文摘Several studies have suggested that exogenous glial cell line-derived neurotrophic factor may pro-tect neurons from cerebral ischemic injury. However, the mechanisms underlying the neuroprotec-tive effects of endogenous glial cell line-derived neurotrophic factor remain unclear. The present experiments sought to elucidate the influence of various conditioned media on neuronal apoptosis, using a normal culture medium for astrocytes, an astrocyte medium highly expressing glial cell line-derived neurotrophic factor, and an astrocyte medium in which glial cell line-derived neurotro-phic factor expression was silenced using RNAi technology. The results confirmed that the use of RNAi silencing to target pretreated glial cell line-derived neurotrophic factor expression promoted neuronal apoptosis. In addition, oxygen and glucose deprivation preconditioning was found to upregulate glial cell line-derived neurotrophic factor expression, and significantly reduce neuronal apoptosis.
基金the Science and Technology Development Program of Shandong Province, No.032050116the Natural Science Foundation of Shandong Province,No.ZR2010HM077the 20 Staff Foundation of 1020 Project of Shandong Province
文摘This study investigated the neuroprotective effect of Yiqi Bushen prescription (YQBS, supplementing qi and tonifying kidney) on neuronal cell apoptosis. Following YQBS treatment, the number of surviving hippocampal neurons increased, anti-apoptotic Bcl-2 expression increased and pro-apoptotic Bax expression decreased. In addition, diabetic rats exhibited improved learning and memory. YQBS treatment also increased Bcl-2 mRNA expression and the ratio of Bcl-2/Bax, but decreased levels of hypoxia-inducible factor-1α mRNA and Bax mRNA expression after high-glucose/hypoxia-induced injury. Results demonstrated that YQBS inhibited hippocampal neuronal apoptosis by decreasing hypoxia-inducible factor-1α expression and increasing Bcl-2 expression, thereby improving cognitive impairment in diabetic rats.
