Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotectiv...Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.展开更多
Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promo...Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.展开更多
BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a the...BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.展开更多
Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavio...Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice.Mice were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein groups.In the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse brain.These changes resulted in improved neurological function compared with controlled cortical impact mice.Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein.Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral outcomes.Furthermore,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control.Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways.展开更多
Traumatic brain injury(TBI)is the main cause of disability,mental health disorder,and even death,with its incidence and social costs rising steadily.Although different treatment strategies have been developed and test...Traumatic brain injury(TBI)is the main cause of disability,mental health disorder,and even death,with its incidence and social costs rising steadily.Although different treatment strategies have been developed and tested to mitigate neurological decline,a definitive cure for these conditions remains elusive.Studies have revealed that vari-ous neurotrophins represented by the brain-derived neurotrophic factor are the key regulators of neuroinflammation,apoptosis,blood-brain barrier permeability,neurite regeneration,and memory function.These factors are instrumental in alleviating neu-roinflammation and promoting neuroregeneration.In addition,neural stem cells(NSC)contribute to nerve repair through inherent neuroprotective and immunomodulatory properties,the release of neurotrophins,the activation of endogenous NSCs,and in-tercellular signaling.Notably,innovative research proposals are emerging to combine BDNF and NSCs,enabling them to synergistically complement and promote each other in facilitating injury repair and improving neuron differentiation after TBI.In this review,we summarize the mechanism of neurotrophins in promoting neurogen-esis and restoring neural function after TBI,comprehensively explore the potential therapeutic effects of various neurotrophins in basic research on TBI,and investigate their interaction with NSCs.This endeavor aims to provide a valuable insight into the clinical treatment and transformation of neurotrophins in TBI,thereby promoting the progress of TBI therapeutics.展开更多
Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia,but the underlying mechanism has not yet been fully elucidated.Studies have shown that autophagy plays an important role in...Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia,but the underlying mechanism has not yet been fully elucidated.Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment,and the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway plays an important role in autophagy regulation.To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models,we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method.Starting at 2 hours after modeling,electroacupuncture was delivered at the Shenting(GV24)and Baihui(GV20)acupoints,with a dilatational wave(1-20 Hz frequency,2 mA intensity,6 V peak voltage),for 30 minutes/day over 8 consecutive days.Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury,increased the mRNA expression levels of the PI3K/Akt signaling pathwayrelated factors Beclin-1,mammalian target of rapamycin(mTOR),and PI3K,increased the protein expression levels of phosphorylated Akt,Beclin-1,PI3K,and mTOR in the ischemic cerebral cortex,and simultaneously reduced p53 mRNA and protein expression levels.In the Morris water maze test,the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.In the spatial probe test,the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.Electroacupuncture stimulation applied to the Shenting(GV24)and Baihui(GV20)acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment.This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,China(approval No.8150150901)on March 10,2016.展开更多
Epidural electrical stimulation can restore limb motor function after spinal cord injury by reactivating the surviving neural circuits.In previous epidural electrical stimulation studies,single electrode sites and con...Epidural electrical stimulation can restore limb motor function after spinal cord injury by reactivating the surviving neural circuits.In previous epidural electrical stimulation studies,single electrode sites and continuous tetanic stimulation have often been used.With this stimulation,the body is prone to declines in tolerance and locomotion coordination.In the present study,rat models of complete spinal cord injury were established by vertically cutting the spinal cord at the T8 level to eliminate disturbance from residual nerve fibers,and were then subjected to epidural electrical stimulation.The flexible extradural electrode had good anatomical topology and matched the shape of the spinal canal of the implanted segment.Simultaneously,the electrode stimulation site was able to be accurately applied to the L2–3 and S1 segments of the spinal cord.To evaluate the biocompatibility of the implanted epidural electrical stimulation electrodes,GFAP/Iba-1 doublelabeled immunofluorescence staining was performed on the spinal cord below the electrodes at 7 days after the electrode implantation.Immunofluorescence results revealed no significant differences in the numbers or morphologies of microglia and astrocytes in the spinal cord after electrode implantation,and there was no activated Iba-1~+cell aggregation,indicating that the implant did not cause an inflammatory response in the spinal cord.Rat gait analysis showed that,at 3 days after surgery,gait became coordinated in rats with spinal cord injury under burst stimulation.The regained locomotion could clearly distinguish the support phase and the swing phase and dynamically adjust with the frequency of stimulus distribution.To evaluate the matching degree between the flexible epidural electrode(including three stimulation contacts),vertebral morphology,and the level of the epidural site of the stimulation electrode,micro-CT was used to scan the thoracolumbar vertebrae of rats before and after electrode implantation.Based on the experimental results of gait recovery using three-site stimulation electrodes at L2–3 and S1 combined with burst stimulation in a rat model of spinal cord injury,epidural electrical stimulation is a promising protocol that needs to be further explored.This study was approved by the Animal Ethics Committee of Chinese PLA General Hospital(approval No.2019-X15-39)on April 19,2019.展开更多
Stroke is a main cause of death and disability worldwide.The ability of the brain to selfrepair in the acute and chronic phases after stroke is minimal;however,promising stem cell-based interventions are emerging that...Stroke is a main cause of death and disability worldwide.The ability of the brain to selfrepair in the acute and chronic phases after stroke is minimal;however,promising stem cell-based interventions are emerging that may give substantial and possibly complete recovery of brain function after stroke.Many animal models and clinical trials have demonstrated that neural stem cells(NSCs)in the central nervous system can orchestrate neurological repair through nerve regeneration,neuron polarization,axon pruning,neurite outgrowth,repair of myelin,and remodeling of the microenvironment and brain networks.Compared with other types of stem cells,NSCs have unique advantages in cell replacement,paracrine action,inflammatory regulation and neuroprotection.Our review summarizes NSC origins,characteristics,therapeutic mechanisms and repair processes,then highlights current research findings and clinical evidence for NSC therapy.These results may be helpful to inform the direction of future stroke research and to guide clinical decision-making.展开更多
Sensory function is the most significant criterion when evaluating the prognosis of replanted fingers. Current clinical research has focused on surgical techniques and indications for finger replantation; however, few...Sensory function is the most significant criterion when evaluating the prognosis of replanted fingers. Current clinical research has focused on surgical techniques and indications for finger replantation; however, few studies have focused on recovery of finger sensory function after replantation. This study retrospectively assessed data of eight patients who had undergone nine Zone I replantations of the fingertips in the First Affiliated Hospital of Sun Yat-sen University of China from July 2014 to January 2016. Variations in the extent of damage, with the residual vessels or nerves in some fingers being too short or even missing, prevented tension-free suture repair in some patients. Thus, repair of four of the nine fingertips included arteriovenous anastomosis, the remaining five undergoing arterial anastomosis during replantation of the amputated fingers. Three patients underwent nerve repair, whereas the remaining six cases did not. Fingertip replantations were successful in all eight patients. Compared with the patients without vascular anastomosis, no obvious atrophy was visible in the fingertips of patients who did undergo vascular anastomosis during replantation and their sensory function did recover. Fingertip replantation provides good sensory function and cosmetic outcomes when good artery and vein anastomoses have been created, even when digital nerves have not been repaired.展开更多
Functional electrical stimulation is an effective way to rebuild hindlimb motor function after spinal cord injury.However,no site map exists to serve as a reference for implanting stimulator electrodes.In this study,r...Functional electrical stimulation is an effective way to rebuild hindlimb motor function after spinal cord injury.However,no site map exists to serve as a reference for implanting stimulator electrodes.In this study,rat models of thoracic spinal nerve 9 contusion were established by a heavy-impact method and rat models of T6/8/9 spinal cord injury were established by a transection method.Intraspinal microstimulation was performed to record motion types,site coordinates,and threshold currents induced by stimulation.After transection(complete injury),the core region of hip flexion migrated from the T13 to T12 vertebral segment,and the core region of hip extension migrated from the L1 to T13 vertebral segment.Migration was affected by post-transection time,but not transection segment.Moreover,the longer the post-transection time,the longer the distance of migration.This study provides a reference for spinal electrode implantation after spinal cord injury.This study was approved by the Institutional Animal Care and Use Committee of Nantong University,China(approval No.20190225-008)on February 26,2019.展开更多
BACKGROUND As a cellular mode of therapy,bone marrow mesenchymal stem cells(BMSCs)are used to treat stroke.However,their mechanisms in stroke treatment have not been established.Recent evidence suggests that regulatio...BACKGROUND As a cellular mode of therapy,bone marrow mesenchymal stem cells(BMSCs)are used to treat stroke.However,their mechanisms in stroke treatment have not been established.Recent evidence suggests that regulation of dysregulated gut flora after stroke affects stroke outcomes.AIM To investigate the effects of BMSCs on gut microbiota after ischemic stroke.METHODS A total of 30 Sprague-Dawley rats were randomly divided into three groups,including sham operation control group,transient middle cerebral artery occlusion(MCAO)group,and MCAO with BMSC treatment group.The modified Neurological Severity Score(mNSS),beam walking test,and Morris water maze test were used to evaluate neurological function recovery after BMSC transplantation.Nissl staining was performed to elucidate on the pathology of nerve cells in the hippocampus.Feces from each group of rats were collected and analyzed by 16s rDNA sequencing.RESULTS BMSC transplantation significantly reduced mNSS(P<0.01).Rats performed better in the beam walking test in the BMSC group than in the MCAO group(P<0.01).The Morris water maze test revealed that the BMSC treatment group exhibited a significant improvement in learning and memory.Nissl staining for neuronal damage assessment after stroke showed that in the BMSC group,cells were orderly arranged with significantly reduced necrosis.Moreover,BMSCs regulated microbial structure composition.In rats treated with BMSCs,the abundance of potential short-chain fatty acid producing bacteria and Lactobacillus was increased.CONCLUSION BMSC transplantation is a potential therapeutic option for ischemic stroke,and it promotes neurological functions by regulating gut microbiota dysbiosis.展开更多
Diabetes mellitus is an independent risk factor for ischemic stroke.Both diabetes mellitus and stroke are linked to systemic inflammation that aggravates patient outcomes.Stellate ganglion block can effectively regula...Diabetes mellitus is an independent risk factor for ischemic stroke.Both diabetes mellitus and stroke are linked to systemic inflammation that aggravates patient outcomes.Stellate ganglion block can effectively regulate the inflammatory response.Therefore,it is hypothesized that stellate ganglion block could be a potential therapy for ischemic stroke in diabetic subjects.In this study,we induced diabetes mellitus in rats by feeding them a high-fat diet for 4 successive weeks.The left middle cerebral artery was occluded to establish models of ischemic stroke in diabetic rats.Subsequently,we performed left stellate ganglion block with 1%lidocaine using the percutaneous posterior approach 15 minutes before reperfusion and again 20 and 44 hours after reperfusion.Our results showed that stellate ganglion block did not decrease the blood glucose level in diabetic rats with diabetes mellitus but did reduce the cerebral infarct volume and the cerebral water content.It also improved the recovery of neurological function,increased 28-day survival rate,inhibited Toll like receptor 4/nuclear factor kappa B signaling pathway and reduced inflammatory response in the plasma of rats.However,injection of Toll like receptor 4 agonist lipopolysaccharide 5 minutes before stellate ganglion block inhibited the effect of stellate ganglion block,whereas injection of Toll like receptor 4 inhibitor TAK242 had no such effect.We also found that stellate ganglion block performed at night had no positive effect on diabetic ischemic stroke.These findings suggest that stellate ganglion block is a potential therapy for diabetic ischemic stroke and that it may be mediated through the Toll like receptor 4/nuclear factor kappa B signaling pathway.We also found that the therapeutic effect of stellate ganglion block is affected by circadian rhythm.展开更多
Objective: To investigate the effects of butyphthalide + alteplase (rt-PA) intravenous thrombolysis on the diffusion-weighted imaging (DWI) characteristics, coagulation function and neurological function in patients w...Objective: To investigate the effects of butyphthalide + alteplase (rt-PA) intravenous thrombolysis on the diffusion-weighted imaging (DWI) characteristics, coagulation function and neurological function in patients with acute cerebral infarction. Methods: The patients with acute cerebral infarction who were admitted to our hospital between April 2015 and October 2018 and with the onset time 4.5 hours were selected and divided into the observation group receiving butyphthalide + rt-PA intravenous thrombolysis and the control group receiving rt-PA intravenous thrombolysis by random number table. The differences in DWI parameter apparent diffusion coefficient (ADC), coagulation function indexes and neurological function indexes were compared between the two groups. Results: At 7 and 14 days after treatment, the ADC values of both groups were significantly increased, and the ADC values of the observation group were significantly higher than those of the control group;at 7 days after treatment, the prothrombin time (PT) and activated partial thromboplastin time (APTT) levels in both groups were significantly prolonged whereas fibrinogen (FIB), D-dimer (D-D), platelet activating factor (PAF), P-selectin, von Willebrand factor (vWF), neuron-specific enolase (NSE), S100B protein (S100B), malondialdehyde (MDA) and endothelin-1 (ET-1) contents were significantly decreased, and the APTT and PT levels in the observation group were significantly shorter than those in the control group whereas FIB, D-D, PAF, P-selectin, vWF, NSE, S100B, MDA and ET-1 contents were significantly lower than those in the control group. Conclusion: Butyphthalide + rt-PA intravenous thrombolysis can improve the DWI characteristics, coagulation function and neurological function of patients with acute cerebral infarction.展开更多
Objective:To investigate the effects of intravenous thrombolysis therapy with alteplase on neurological function,coagulation function and serum inflammatory factors in patients with acute cerebral infarction.Methods:A...Objective:To investigate the effects of intravenous thrombolysis therapy with alteplase on neurological function,coagulation function and serum inflammatory factors in patients with acute cerebral infarction.Methods:A total of 96 patients with acute cerebral infarction admitted to our hospital from September 2017 to October 2019 were randomly divided into two groups,with 48 patients in each group.The control group(n=48)received routine treatment,and the observation group received intravenous thrombolysis therapy with alteplase on the basis of routine treatment.The neurological deficit score,prothrombin time(PT),activated partial thromboplastin time(APTT),tumor necrosis factor-a level(TNF-α),and high-sensitivity C-reactive protein(hs-CRP)were compared between the two groups after 15 days of treatment.Results:After treatment,NIHSS scores in both groups were lower than those before treatment;PT levels were increased,while APTT,TNF-αand hs-CRP levels were all decreased in both groups,and the changes in the observation group were greater than those in the control group,with statistically significant difference(P<0.05).Conclusions:Intravenous thrombolysis therapy with alteplase can improve the neurological function,coagulation function and serum levels of inflammatory factors in patients with acute cerebral infarction,which is worthy of clinical application.展开更多
Early intervention with bone marrow mesenchymal stem cells to change the form and function of the gut microbiota may help rats regain neurological function after a stroke.
Objective:To study the sedative effect of dexmedetomidine in elderly patients with prostate cancer undergoing three hole LRP,and its effect on nerve function and brain oxygen metabolism.Methods:From August 2016 to Dec...Objective:To study the sedative effect of dexmedetomidine in elderly patients with prostate cancer undergoing three hole LRP,and its effect on nerve function and brain oxygen metabolism.Methods:From August 2016 to December 2019,78 patients with LRP under general anesthesia in our hospital were randomly selected and divided into control group and observation group according to the random number table method,39 cases in each group.During the operation,the observation group was given dextromethoridine,while the control group was given the same amount of normal saline.The changes of cognitive function index(MoCA score,POCD incidence rate),neurological function index(TGF-β1,NSE,IGF-1),brain oxygen metabolism index(PaO2,map,PaCO2,rSO2)before and after operation were compared between the two groups.The visual analogue score(VAS),the amount of analgesic drugs and the times of pressing the analgesic pump were compared between the two groups.The incidence of adverse reactions was compared between the two groups.Results:Before operation,there was no significant difference in cognitive function index,neurological function index and brain oxygen metabolism index between the two groups(P>0.05).On the first and third days after operation,MOCA score of the two groups was significantly lower,MOCA score of the observation group was significantly higher than that of the control group,POCD incidence of the observation group was significantly lower than that of the control group;on the third day after operation,TGF-β1 and IGF-1 of the two groups were significantly lower,TGF-β1 and IGF-1 of the observation group were significantly lower-The NSE in the observation group was significantly lower than that in the control group(P<0.05).In this study,1 hour after the establishment of pneumoperitoneum,PaCO2 and rSO2 in the two groups were significantly increased,6 hours and 12 hours after the operation,the VAS score of the observation group was lower than that of the control group,and the dosage of analgesic pump and the number of times of compression of the analgesic pump were significantly lower than that of the control group(P<0.05).There was no difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:DEX has a good sedative effect on the elderly prostate cancer patients undergoing LRP with three hole method.It has little effect on nerve function and brain oxygen metabolism,and has a good safety.展开更多
Objective To study the effect and mechanism of neurological function recovery in rats with spinal cord injury ( SCI) rats after transplantation of neural stem cells which are directly differentiated from bone marrow m...Objective To study the effect and mechanism of neurological function recovery in rats with spinal cord injury ( SCI) rats after transplantation of neural stem cells which are directly differentiated from bone marrow mesenchymal stem cells ( BMSC ) ,and to investigate the suitable engraftment time. Methods BMSC at 3rd passage were differentiated into neural stem cells ( NSC) , and immunofluorescence staining was used to展开更多
Exosomes derived from human bone marrow mesenchymal stem cells(MSC-Exo)are characterized by easy expansion and storage,low risk of tumor formation,low immunogenicity,and anti-inflammatory effects.The therapeutic effec...Exosomes derived from human bone marrow mesenchymal stem cells(MSC-Exo)are characterized by easy expansion and storage,low risk of tumor formation,low immunogenicity,and anti-inflammatory effects.The therapeutic effects of MSC-Exo on ischemic stroke have been widely explored.However,the underlying mechanism remains unclear.In this study,we established a mouse model of ischemic brain injury induced by occlusion of the middle cerebral artery using the thread bolt method and injected MSC-Exo into the tail vein.We found that administration of MSC-Exo reduced the volume of cerebral infarction in the ischemic brain injury mouse model,increased the levels of interleukin-33(IL-33)and suppression of tumorigenicity 2 receptor(ST2)in the penumbra of cerebral infarction,and improved neurological function.In vitro results showed that astrocyte-conditioned medium of cells deprived of both oxygen and glucose,to simulate ischemia conditions,combined with MSC-Exo increased the survival rate of primary cortical neurons.However,after transfection by IL-33 siRNA or ST2 siRNA,the survival rate of primary cortical neurons was markedly decreased.These results indicated that MSC-Exo inhibited neuronal death induced by oxygen and glucose deprivation through the IL-33/ST2 signaling pathway in astrocytes.These findings suggest that MSC-Exo may reduce ischemia-induced brain injury through regulating the IL-33/ST2 signaling pathway.Therefore,MSC-Exo may be a potential therapeutic method for ischemic stroke.展开更多
In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly unders...In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.展开更多
Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a ...Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81871785 and 81672161(both to ZSY)。
文摘Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.
基金supported by the National Natural Science Foundation of China,Nos.81801169 (to LXX),82071404 (to HC),81870952 (to HMW)。
文摘Promotion of new blood vessel formation is a new strategy for treating ischemic stroke.Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke.miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model,while its effect on ischemic stroke remains elusive.In this study,we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell prolife ration and enhanced angiogenesis.In rat models of focal cerebral ischemia,ove rexpression of miR-181b reduced infarction volume,promoted angiogenesis in ischemic penumbra,and improved neurological function.We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3’-UTR of phosphatase and tensin homolog(PTEN) mRNA to induce PTEN downregulation,leading to activation of the protein kinase B(Akt) pathway,upregulated expression of vascular endothelial growth facto rs,down-regulated expression of endostatin,and promoted angiogenesis.Taken togethe r,these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stro ke through activating the PTEN/Akt signal pathway and promoting angiogenesis.
基金This study was approved by the Ethic Committee of Basic Medical College of Qingdao University(Approval No.QDWMkj-2020-012).
文摘BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.
基金supported by the National Natural Science Foundation of China,Nos.81801236(to ZX),81974189(to HT)a grant from Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.ynlc201719(to QZ).
文摘Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are unclear.This study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in mice.Mice were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein groups.In the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse brain.These changes resulted in improved neurological function compared with controlled cortical impact mice.Western blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent protein.Synchrotron radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral outcomes.Furthermore,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a control.Mechanistic analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways.
基金Laboratory Animal Foundation Program of Military,Grant/Award Number:SYDW[2018]01Promotion Plan of the Air Force Medical University,Grant/Award Number:2020SWAQ11Shaanxi Province Innovation Capability Support Plan,Grant/Award Number:2021PT-037。
文摘Traumatic brain injury(TBI)is the main cause of disability,mental health disorder,and even death,with its incidence and social costs rising steadily.Although different treatment strategies have been developed and tested to mitigate neurological decline,a definitive cure for these conditions remains elusive.Studies have revealed that vari-ous neurotrophins represented by the brain-derived neurotrophic factor are the key regulators of neuroinflammation,apoptosis,blood-brain barrier permeability,neurite regeneration,and memory function.These factors are instrumental in alleviating neu-roinflammation and promoting neuroregeneration.In addition,neural stem cells(NSC)contribute to nerve repair through inherent neuroprotective and immunomodulatory properties,the release of neurotrophins,the activation of endogenous NSCs,and in-tercellular signaling.Notably,innovative research proposals are emerging to combine BDNF and NSCs,enabling them to synergistically complement and promote each other in facilitating injury repair and improving neuron differentiation after TBI.In this review,we summarize the mechanism of neurotrophins in promoting neurogen-esis and restoring neural function after TBI,comprehensively explore the potential therapeutic effects of various neurotrophins in basic research on TBI,and investigate their interaction with NSCs.This endeavor aims to provide a valuable insight into the clinical treatment and transformation of neurotrophins in TBI,thereby promoting the progress of TBI therapeutics.
基金supported by the National Natural Science Foundation of China,No.81574042the Traditional Chinese Medicine Special Research Projects of Henan Province of China,No.2018JDZX011(both to XDF).
文摘Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia,but the underlying mechanism has not yet been fully elucidated.Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment,and the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway plays an important role in autophagy regulation.To investigate the role played by the PI3K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models,we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method.Starting at 2 hours after modeling,electroacupuncture was delivered at the Shenting(GV24)and Baihui(GV20)acupoints,with a dilatational wave(1-20 Hz frequency,2 mA intensity,6 V peak voltage),for 30 minutes/day over 8 consecutive days.Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury,increased the mRNA expression levels of the PI3K/Akt signaling pathwayrelated factors Beclin-1,mammalian target of rapamycin(mTOR),and PI3K,increased the protein expression levels of phosphorylated Akt,Beclin-1,PI3K,and mTOR in the ischemic cerebral cortex,and simultaneously reduced p53 mRNA and protein expression levels.In the Morris water maze test,the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.In the spatial probe test,the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation.Electroacupuncture stimulation applied to the Shenting(GV24)and Baihui(GV20)acupoints activated the PI3K/Akt signaling pathway and improved rat learning and memory impairment.This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,China(approval No.8150150901)on March 10,2016.
基金supported by the National Natural Science Foundation of China,Nos.81601052(to XRJ),81520108017(to PFT)the Beijing Nova Program of Science and Technology of China,No.2018034(to XRJ)+1 种基金the Beijing Municipal Science and Technology Project of China,No.D16100002816005(to PFT)the Subsidiary of PLA Major Project of China,No.AWS17J004(to PFT)。
文摘Epidural electrical stimulation can restore limb motor function after spinal cord injury by reactivating the surviving neural circuits.In previous epidural electrical stimulation studies,single electrode sites and continuous tetanic stimulation have often been used.With this stimulation,the body is prone to declines in tolerance and locomotion coordination.In the present study,rat models of complete spinal cord injury were established by vertically cutting the spinal cord at the T8 level to eliminate disturbance from residual nerve fibers,and were then subjected to epidural electrical stimulation.The flexible extradural electrode had good anatomical topology and matched the shape of the spinal canal of the implanted segment.Simultaneously,the electrode stimulation site was able to be accurately applied to the L2–3 and S1 segments of the spinal cord.To evaluate the biocompatibility of the implanted epidural electrical stimulation electrodes,GFAP/Iba-1 doublelabeled immunofluorescence staining was performed on the spinal cord below the electrodes at 7 days after the electrode implantation.Immunofluorescence results revealed no significant differences in the numbers or morphologies of microglia and astrocytes in the spinal cord after electrode implantation,and there was no activated Iba-1~+cell aggregation,indicating that the implant did not cause an inflammatory response in the spinal cord.Rat gait analysis showed that,at 3 days after surgery,gait became coordinated in rats with spinal cord injury under burst stimulation.The regained locomotion could clearly distinguish the support phase and the swing phase and dynamically adjust with the frequency of stimulus distribution.To evaluate the matching degree between the flexible epidural electrode(including three stimulation contacts),vertebral morphology,and the level of the epidural site of the stimulation electrode,micro-CT was used to scan the thoracolumbar vertebrae of rats before and after electrode implantation.Based on the experimental results of gait recovery using three-site stimulation electrodes at L2–3 and S1 combined with burst stimulation in a rat model of spinal cord injury,epidural electrical stimulation is a promising protocol that needs to be further explored.This study was approved by the Animal Ethics Committee of Chinese PLA General Hospital(approval No.2019-X15-39)on April 19,2019.
基金This work was supported by the National Natural Science Foundation of China,No.81471308(to JL)Program of China National Health Commission and National Medical Products Administration(NMPA),No.CMR-20161129-1003(to JL)+1 种基金Liaoning Province Excellent Talent Program Project,No.XLYC1902031(to JL)Dalian Innovation Fund,No.2018J11CY025(to JL).
文摘Stroke is a main cause of death and disability worldwide.The ability of the brain to selfrepair in the acute and chronic phases after stroke is minimal;however,promising stem cell-based interventions are emerging that may give substantial and possibly complete recovery of brain function after stroke.Many animal models and clinical trials have demonstrated that neural stem cells(NSCs)in the central nervous system can orchestrate neurological repair through nerve regeneration,neuron polarization,axon pruning,neurite outgrowth,repair of myelin,and remodeling of the microenvironment and brain networks.Compared with other types of stem cells,NSCs have unique advantages in cell replacement,paracrine action,inflammatory regulation and neuroprotection.Our review summarizes NSC origins,characteristics,therapeutic mechanisms and repair processes,then highlights current research findings and clinical evidence for NSC therapy.These results may be helpful to inform the direction of future stroke research and to guide clinical decision-making.
基金supported by a grant from the Department of Health of Guangdong Province of China,No.A2016018the Specialized Research Fund for the Doctoral Program of Higher Education,No.20120171120075+3 种基金a grant from the Science and Technology Project of Guangdong Province of China,No.2014A020212479a grant from the Science and Technology Project of Guangdong Province of China,No.2016A010103012a grant from the Science and Technology Program of Guangzhou City of China,No.201300000174a grant from the Doctoral Start-up Project of the Natural Science Foundation of Guangdong Province of China,No.2017A030310302
文摘Sensory function is the most significant criterion when evaluating the prognosis of replanted fingers. Current clinical research has focused on surgical techniques and indications for finger replantation; however, few studies have focused on recovery of finger sensory function after replantation. This study retrospectively assessed data of eight patients who had undergone nine Zone I replantations of the fingertips in the First Affiliated Hospital of Sun Yat-sen University of China from July 2014 to January 2016. Variations in the extent of damage, with the residual vessels or nerves in some fingers being too short or even missing, prevented tension-free suture repair in some patients. Thus, repair of four of the nine fingertips included arteriovenous anastomosis, the remaining five undergoing arterial anastomosis during replantation of the amputated fingers. Three patients underwent nerve repair, whereas the remaining six cases did not. Fingertip replantations were successful in all eight patients. Compared with the patients without vascular anastomosis, no obvious atrophy was visible in the fingertips of patients who did undergo vascular anastomosis during replantation and their sensory function did recover. Fingertip replantation provides good sensory function and cosmetic outcomes when good artery and vein anastomoses have been created, even when digital nerves have not been repaired.
基金supported by the National Natural Science Foundation of China,No.61534003(to ZGW),81371663(to XYS)Opening Project of State Key Laboratory of Bioelectronics in Southeast University(to XYS)+2 种基金the“226 Engineering”Research Project of Nantong Government(to XYS)“Six Talent Peaks”Project,No.SWYY-116(to XYS)Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.KYCX18_2424(to CLT)。
文摘Functional electrical stimulation is an effective way to rebuild hindlimb motor function after spinal cord injury.However,no site map exists to serve as a reference for implanting stimulator electrodes.In this study,rat models of thoracic spinal nerve 9 contusion were established by a heavy-impact method and rat models of T6/8/9 spinal cord injury were established by a transection method.Intraspinal microstimulation was performed to record motion types,site coordinates,and threshold currents induced by stimulation.After transection(complete injury),the core region of hip flexion migrated from the T13 to T12 vertebral segment,and the core region of hip extension migrated from the L1 to T13 vertebral segment.Migration was affected by post-transection time,but not transection segment.Moreover,the longer the post-transection time,the longer the distance of migration.This study provides a reference for spinal electrode implantation after spinal cord injury.This study was approved by the Institutional Animal Care and Use Committee of Nantong University,China(approval No.20190225-008)on February 26,2019.
基金National Natural Science Foundation of China,No.81774059 and No.82074533Tianjin Natural Science Foundation,No.19JCZDJC37100.
文摘BACKGROUND As a cellular mode of therapy,bone marrow mesenchymal stem cells(BMSCs)are used to treat stroke.However,their mechanisms in stroke treatment have not been established.Recent evidence suggests that regulation of dysregulated gut flora after stroke affects stroke outcomes.AIM To investigate the effects of BMSCs on gut microbiota after ischemic stroke.METHODS A total of 30 Sprague-Dawley rats were randomly divided into three groups,including sham operation control group,transient middle cerebral artery occlusion(MCAO)group,and MCAO with BMSC treatment group.The modified Neurological Severity Score(mNSS),beam walking test,and Morris water maze test were used to evaluate neurological function recovery after BMSC transplantation.Nissl staining was performed to elucidate on the pathology of nerve cells in the hippocampus.Feces from each group of rats were collected and analyzed by 16s rDNA sequencing.RESULTS BMSC transplantation significantly reduced mNSS(P<0.01).Rats performed better in the beam walking test in the BMSC group than in the MCAO group(P<0.01).The Morris water maze test revealed that the BMSC treatment group exhibited a significant improvement in learning and memory.Nissl staining for neuronal damage assessment after stroke showed that in the BMSC group,cells were orderly arranged with significantly reduced necrosis.Moreover,BMSCs regulated microbial structure composition.In rats treated with BMSCs,the abundance of potential short-chain fatty acid producing bacteria and Lactobacillus was increased.CONCLUSION BMSC transplantation is a potential therapeutic option for ischemic stroke,and it promotes neurological functions by regulating gut microbiota dysbiosis.
基金The study was approved by Postdoctoral Scientific Research Developmental Fund of Heilongjiang Province,No.LBH-Q18074(to WCY).
文摘Diabetes mellitus is an independent risk factor for ischemic stroke.Both diabetes mellitus and stroke are linked to systemic inflammation that aggravates patient outcomes.Stellate ganglion block can effectively regulate the inflammatory response.Therefore,it is hypothesized that stellate ganglion block could be a potential therapy for ischemic stroke in diabetic subjects.In this study,we induced diabetes mellitus in rats by feeding them a high-fat diet for 4 successive weeks.The left middle cerebral artery was occluded to establish models of ischemic stroke in diabetic rats.Subsequently,we performed left stellate ganglion block with 1%lidocaine using the percutaneous posterior approach 15 minutes before reperfusion and again 20 and 44 hours after reperfusion.Our results showed that stellate ganglion block did not decrease the blood glucose level in diabetic rats with diabetes mellitus but did reduce the cerebral infarct volume and the cerebral water content.It also improved the recovery of neurological function,increased 28-day survival rate,inhibited Toll like receptor 4/nuclear factor kappa B signaling pathway and reduced inflammatory response in the plasma of rats.However,injection of Toll like receptor 4 agonist lipopolysaccharide 5 minutes before stellate ganglion block inhibited the effect of stellate ganglion block,whereas injection of Toll like receptor 4 inhibitor TAK242 had no such effect.We also found that stellate ganglion block performed at night had no positive effect on diabetic ischemic stroke.These findings suggest that stellate ganglion block is a potential therapy for diabetic ischemic stroke and that it may be mediated through the Toll like receptor 4/nuclear factor kappa B signaling pathway.We also found that the therapeutic effect of stellate ganglion block is affected by circadian rhythm.
基金Major Project of Shanghai Science and Technology Commission (Sub-project) No: 11411950300
文摘Objective: To investigate the effects of butyphthalide + alteplase (rt-PA) intravenous thrombolysis on the diffusion-weighted imaging (DWI) characteristics, coagulation function and neurological function in patients with acute cerebral infarction. Methods: The patients with acute cerebral infarction who were admitted to our hospital between April 2015 and October 2018 and with the onset time 4.5 hours were selected and divided into the observation group receiving butyphthalide + rt-PA intravenous thrombolysis and the control group receiving rt-PA intravenous thrombolysis by random number table. The differences in DWI parameter apparent diffusion coefficient (ADC), coagulation function indexes and neurological function indexes were compared between the two groups. Results: At 7 and 14 days after treatment, the ADC values of both groups were significantly increased, and the ADC values of the observation group were significantly higher than those of the control group;at 7 days after treatment, the prothrombin time (PT) and activated partial thromboplastin time (APTT) levels in both groups were significantly prolonged whereas fibrinogen (FIB), D-dimer (D-D), platelet activating factor (PAF), P-selectin, von Willebrand factor (vWF), neuron-specific enolase (NSE), S100B protein (S100B), malondialdehyde (MDA) and endothelin-1 (ET-1) contents were significantly decreased, and the APTT and PT levels in the observation group were significantly shorter than those in the control group whereas FIB, D-D, PAF, P-selectin, vWF, NSE, S100B, MDA and ET-1 contents were significantly lower than those in the control group. Conclusion: Butyphthalide + rt-PA intravenous thrombolysis can improve the DWI characteristics, coagulation function and neurological function of patients with acute cerebral infarction.
文摘Objective:To investigate the effects of intravenous thrombolysis therapy with alteplase on neurological function,coagulation function and serum inflammatory factors in patients with acute cerebral infarction.Methods:A total of 96 patients with acute cerebral infarction admitted to our hospital from September 2017 to October 2019 were randomly divided into two groups,with 48 patients in each group.The control group(n=48)received routine treatment,and the observation group received intravenous thrombolysis therapy with alteplase on the basis of routine treatment.The neurological deficit score,prothrombin time(PT),activated partial thromboplastin time(APTT),tumor necrosis factor-a level(TNF-α),and high-sensitivity C-reactive protein(hs-CRP)were compared between the two groups after 15 days of treatment.Results:After treatment,NIHSS scores in both groups were lower than those before treatment;PT levels were increased,while APTT,TNF-αand hs-CRP levels were all decreased in both groups,and the changes in the observation group were greater than those in the control group,with statistically significant difference(P<0.05).Conclusions:Intravenous thrombolysis therapy with alteplase can improve the neurological function,coagulation function and serum levels of inflammatory factors in patients with acute cerebral infarction,which is worthy of clinical application.
文摘Early intervention with bone marrow mesenchymal stem cells to change the form and function of the gut microbiota may help rats regain neurological function after a stroke.
基金Science and research projects of science and technology commission Shanghai municipality(No.19ZR1408000)
文摘Objective:To study the sedative effect of dexmedetomidine in elderly patients with prostate cancer undergoing three hole LRP,and its effect on nerve function and brain oxygen metabolism.Methods:From August 2016 to December 2019,78 patients with LRP under general anesthesia in our hospital were randomly selected and divided into control group and observation group according to the random number table method,39 cases in each group.During the operation,the observation group was given dextromethoridine,while the control group was given the same amount of normal saline.The changes of cognitive function index(MoCA score,POCD incidence rate),neurological function index(TGF-β1,NSE,IGF-1),brain oxygen metabolism index(PaO2,map,PaCO2,rSO2)before and after operation were compared between the two groups.The visual analogue score(VAS),the amount of analgesic drugs and the times of pressing the analgesic pump were compared between the two groups.The incidence of adverse reactions was compared between the two groups.Results:Before operation,there was no significant difference in cognitive function index,neurological function index and brain oxygen metabolism index between the two groups(P>0.05).On the first and third days after operation,MOCA score of the two groups was significantly lower,MOCA score of the observation group was significantly higher than that of the control group,POCD incidence of the observation group was significantly lower than that of the control group;on the third day after operation,TGF-β1 and IGF-1 of the two groups were significantly lower,TGF-β1 and IGF-1 of the observation group were significantly lower-The NSE in the observation group was significantly lower than that in the control group(P<0.05).In this study,1 hour after the establishment of pneumoperitoneum,PaCO2 and rSO2 in the two groups were significantly increased,6 hours and 12 hours after the operation,the VAS score of the observation group was lower than that of the control group,and the dosage of analgesic pump and the number of times of compression of the analgesic pump were significantly lower than that of the control group(P<0.05).There was no difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:DEX has a good sedative effect on the elderly prostate cancer patients undergoing LRP with three hole method.It has little effect on nerve function and brain oxygen metabolism,and has a good safety.
文摘Objective To study the effect and mechanism of neurological function recovery in rats with spinal cord injury ( SCI) rats after transplantation of neural stem cells which are directly differentiated from bone marrow mesenchymal stem cells ( BMSC ) ,and to investigate the suitable engraftment time. Methods BMSC at 3rd passage were differentiated into neural stem cells ( NSC) , and immunofluorescence staining was used to
基金supported by the National Natural Science Foundation of China,No.81971231(to JL)the Natural Science Foundation of Liaoning Province,No.2022-MS-391(to PW)the Scientific Research Project from the Education Department of Liaoning Province,Nos.JYTQN2020011(to PW),LJKQZ2021147(to JL)。
文摘Exosomes derived from human bone marrow mesenchymal stem cells(MSC-Exo)are characterized by easy expansion and storage,low risk of tumor formation,low immunogenicity,and anti-inflammatory effects.The therapeutic effects of MSC-Exo on ischemic stroke have been widely explored.However,the underlying mechanism remains unclear.In this study,we established a mouse model of ischemic brain injury induced by occlusion of the middle cerebral artery using the thread bolt method and injected MSC-Exo into the tail vein.We found that administration of MSC-Exo reduced the volume of cerebral infarction in the ischemic brain injury mouse model,increased the levels of interleukin-33(IL-33)and suppression of tumorigenicity 2 receptor(ST2)in the penumbra of cerebral infarction,and improved neurological function.In vitro results showed that astrocyte-conditioned medium of cells deprived of both oxygen and glucose,to simulate ischemia conditions,combined with MSC-Exo increased the survival rate of primary cortical neurons.However,after transfection by IL-33 siRNA or ST2 siRNA,the survival rate of primary cortical neurons was markedly decreased.These results indicated that MSC-Exo inhibited neuronal death induced by oxygen and glucose deprivation through the IL-33/ST2 signaling pathway in astrocytes.These findings suggest that MSC-Exo may reduce ischemia-induced brain injury through regulating the IL-33/ST2 signaling pathway.Therefore,MSC-Exo may be a potential therapeutic method for ischemic stroke.
基金supported by the National Natural Science Foundation of China,Nos.82171456 (to QY),81971229 (to QY)the Natural Science Foundation of Chongqing,No.cstc2021jcyj-msxmX0263 (to QY)the Postgraduate Research and Innovation Project of Chongqing,Nos.CYB20151 (to QY),CYS19182 (to YC)。
文摘In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.
基金supported by grants from the National Natural Science Foundation of China, Nos. 81930031 (to JNZ), 81720108015 (to JNZ), 81901525 (to SZ), 82101440 (to DDS), 81801234 (to YZ) and 82071389 (to GLY)the Natural Science Foundation of Tianjin, Nos. 20JCQNJC01270 (to JWW), 20JCQNJC00460 (to GLY), 18JCQNJC81000 (to HTR)+4 种基金Scientific Research Project of Tianjin Education Commission (Natural Science), No. 2018KJ052 (to ZWZ)Tianjin Health and Health Committee Science and Technology Project, No. QN20015 (to JWW)the Science & Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2016YD02 (to YW)Tianjin Key Science and Technology Projects of Innovative Drugs and Medical Devices, No. 19ZXYXSY00070 (to YW)the Clinical Research Fundation of Tianjin Medical University, No. 2018kylc002 (to YW)
文摘Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.