Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated ...Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated with specific central nervous system zones or areas, and its prognosis is uncertain. This case study describes a 62-year-old male patient with acquired brain damage of the anterior cingulate cortex as a result of an ischemic event in the territory of the left anterior cerebral artery. Cognitive function was assessed using the neuropsychological executive function and frontal lobe test battery (BANFE-2) as well as other neuropsychological tests. The results show a profile of higher mental functions characterized by the presence of dysexecutive syndrome with marked behavioral alteration and diencephalic amnesia. .展开更多
Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like re...Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.展开更多
Our previous studies have demonstrated that TP53-induced glycolysis and apoptosis regulator(TIGAR)can protect neurons after cerebral ischemia/reperfusion.However,the role of TIGAR in neonatal hypoxic-ischemic brain da...Our previous studies have demonstrated that TP53-induced glycolysis and apoptosis regulator(TIGAR)can protect neurons after cerebral ischemia/reperfusion.However,the role of TIGAR in neonatal hypoxic-ischemic brain damage(HIBD)remains unknown.In the present study,7-day-old Sprague-Dawley rat models of HIBD were established by permanent occlusion of the left common carotid artery followed by 2-hour hypoxia.At 6 days before induction of HIBD,a lentiviral vector containing short hairpin RNA of either TIGAR or gasdermin D(LV-sh_TIGAR or LV-sh_GSDMD)was injected into the left lateral ventricle and striatum.Highly aggressively proliferating immortalized(HAPI)microglial cell models of in vitro HIBD were established by 2-hour oxygen/glucose deprivation followed by 24-hour reoxygenation.Three days before in vitro HIBD induction,HAPI microglial cells were transfected with LV-sh_TIGAR or LV-sh_GSDMD.Our results showed that TIGAR expression was increased in the neonatal rat cortex after HIBD and in HAPI microglial cells after oxygen/glucose deprivation/reoxygenation.Lentivirusmediated TIGAR knockdown in rats markedly worsened pyroptosis and brain damage after hypoxia/ischemia in vivo and in vitro.Application of exogenous nicotinamide adenine dinucleotide phosphate(NADPH)increased the NADPH level and the glutathione/oxidized glutathione ratio and decreased reactive oxygen species levels in HAPI microglial cells after oxygen/glucose deprivation/reoxygenation.Additionally,exogenous NADPH blocked the effects of TIGAR knockdown in neonatal HIBD in vivo and in vitro.These findings show that TIGAR can inhibit microglial pyroptosis and play a protective role in neonatal HIBD.The study was approved by the Animal Ethics Committee of Soochow University of China(approval No.2017LW003)in 2017.展开更多
Neural stem/progenitor cell(NSC) transplantation has been shown to effectively improve neurological function in rats with hypoxic-ischemic brain damage.Vascular endothelial growth factor(VEGF) is a signaling protein t...Neural stem/progenitor cell(NSC) transplantation has been shown to effectively improve neurological function in rats with hypoxic-ischemic brain damage.Vascular endothelial growth factor(VEGF) is a signaling protein that stimulates angiogenesis and improves neural regeneration.We hypothesized that transplantation of VEGF-transfected NSCs would alleviate hypoxic-ischemic brain damage in neonatal rats.We produced and transfected a recombinant lentiviral vector containing the VEGF165 gene into cultured NSCs.The transfected NSCs were transplanted into the left sensorimotor cortex of rats 3 days after hypoxic-ischemic brain damage.Compared with the NSCs group,VEGF m RNA and protein expression levels were increased in the transgene NSCs group,and learning and memory abilities were significantly improved at 30 days.Furthermore,histopathological changes were alleviated in these animals.Our findings indicate that transplantation of VEGF-transfected NSCs may facilitate the recovery of neurological function,and that its therapeutic effectiveness is better than that of unmodified NSCs.展开更多
Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a r...Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a rat model of HIBD,up-regulation of microRNA-325(miR-325)in the pineal gland is responsible for the suppression of Aanat,a key enzyme involved in melatonin synthesis and circadian rhythm regulation.To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD,we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University(Dushuhu Branch)in 2019.We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD.Furthermore,a luciferase reporter gene assay revealed that LIM homeobox 3(LHX3)is a novel downstream target of miR-325.In addition,in miR-325 knock-down mice,the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland.We established a neonatal mouse model of HIBD by performing doublelayer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours.Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions.Finally,we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3.Taken together,our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD.The clinical trial was approved by Institutional Review Board of Children’s Hospital of Soochow University(approval No.2015028)on July 20,2015.Animal experiments were approved by Animal Care and Use Committee,School of Medicine,Soochow University,China(approval No.XD-2016-1)on January 15,2016.展开更多
BACKGROUND: Central nervous system axons regenerate poorly following neonatal hypoxic-ischemic brain damage (HIBD), partly due to inhibitors, such as Nogo-A. Very few studies have addressed the regulation of Nogo-A in...BACKGROUND: Central nervous system axons regenerate poorly following neonatal hypoxic-ischemic brain damage (HIBD), partly due to inhibitors, such as Nogo-A. Very few studies have addressed the regulation of Nogo-A in neonatal rats following HIBD. However, numerous studies have shown that ephedrine accelerates neuronal remodeling and promotes recovery of neural function in neonatal rats following HIBD. OBJECTIVE: To investigate the effects of ephedrine on expression of Nogo-A and synaptophysin in brain tissues of neonatal rats following HIBD. DESIGN, TIME AND SETTING: A completely randomized, controlled study was performed at the Immunohistochemistry Laboratory of the Research Institute of Pediatrics, Children's Hospital of Chongqing Medical University from August 2008 to March 2009. MATERIALS: Ephedrine hydrochloride (Chifeng Pharmaceutical Group, China), rabbit anti-Nogo-A polyclonal antibody (Abcam, UK), and rabbit antisynaptophysin polyclonal antibody (Lab Vision, USA) were used in this study. METHODS: A total of 96 healthy, neonatal, Sprague Dawley rats were randomly assigned to three groups (n = 32): sham operation, HIBD, and ephedrine. The HIBD model was established by permanent occlusion of the left common carotid artery, followed by 2 hours of hypoxia (8% oxygen and 92% nitrogen). In the sham operation group, the left common carotid artery was exposed, but was not ligated or subjected to hypoxia. Rats in the ephedrine group were intraperitoneally injected with ephedrine immediately following HIBD, with 1.5 mg/kg each time. Rats in the sham operation and HIBD groups were injected with an equal volume of saline. All neonatal rats were treated once daily for 7 days. MAIN OUTCOME MEASURES: Histopathological damage to the cortex and hippocampus was determined by hematoxylin-eosin staining. Expression of Nogo-A and synaptophysin was detected using immunohistochemical staining. RESULTS: Neuronal degeneration and edema were observed in the hypoxic-ischemic cortex and hippocampus by hematoxylin-eosin staining. Compared with the sham operation group, the levels of Nogo-A significantly increased in the HIBD group at various time points (P < 0.01). Nogo-A expression was significantly reduced in the ephedrine group compared with the HIBD group (P < 0.01). Synaptophysin expression was significantly decreased in the hypoxic-ischemic cortex, compared with the sham operation group (P < 0.01). Synaptophysin levels were significantly increased in the ephedrine group, compared with the HIBD group (P < 0.01). CONCLUSION: Altered Nogo-A expression was associated with inversely altered synaptophysin expression. The use of ephedrine normalized expression levels of Nogo-A and synaptophysin following HIBD.展开更多
OBJECTIVE: To investigate the effect of endothelial cells on the permeability of blood brain barrier (BBB) after brain injury and its effect mechanism. DATA SOURCES: We searched for the articles of permeability of BBB...OBJECTIVE: To investigate the effect of endothelial cells on the permeability of blood brain barrier (BBB) after brain injury and its effect mechanism. DATA SOURCES: We searched for the articles of permeability of BBB and endothelial cell injury after brain ischemia, which were published between January 1982 and December 2005, with the key words of “cerebral ischemia damage,blood brain barrier ( BBB),permeability,effect of endothelial cell (EC) and its variation mechanism”in English. STUDY SELECTION: The materials were primarily selected. The articles related to the changes in the permeability of BBB and the effect of endothelial cells as well as the change mechanism after cerebral ischemia damage were chosen. Repetitive studies or review articles were excluded. DATA EXTRACTION: Totally 55 related articles were collected, and 35 were excluded due to repetitive or review articles, finally 20 articles were involved. DATA SYNTHESIS: The content or viewpoints of involved literatures were analyzed. Cerebral ischemia had damage for endothelial cells, such as the inflow of a lot of Ca2+, the production of nitrogen monoxide and oxygen free radical, and aggravated destruction of BBB. After acceptors of inflammatory mediators on cerebrovascular endothelial cell membrane, such as histamine, bradykinin , 5-hydroxytryptamine and so on are activated, endothelial cells shrink and the permeability of BBB increases. Its mechanism involves in the inflow of extracellular Ca2+and the release of intracellular Ca2+ in the cells. Glycocalyx molecule on the surface of endothelial cell, having structural polytropy, is the determinative factor of the permeability of BBB. VEGF, intensively increasing the vasopermeability and mainly effecting on postcapillary vein and veinlet, is the strongest known blood vessel permeation reagent. Its chronic overexpression in the brain can lead the destruction of BBB. CONCLUSION: The injury of endothelial cell participants in the pathological mechanism of BBB destruction after cerebral ischemia.展开更多
Acute hypoxic-ischemic brain damage(HIBD)mainly occurs in adults as a result of perioperative cardiac arrest and asphyxia.The benefits of n-3 polyunsaturated fatty acids(n-3 PUFAs)in maintaining brain growth and devel...Acute hypoxic-ischemic brain damage(HIBD)mainly occurs in adults as a result of perioperative cardiac arrest and asphyxia.The benefits of n-3 polyunsaturated fatty acids(n-3 PUFAs)in maintaining brain growth and development are well documented.However,possible protective targets and underlying mechanisms of mfat-1 mice on HIBD require further investigation.The mfat-1 transgenic mice exhibited protective effects on HIBD,as indicated by reduced infarct range and improved neurobehavioral defects.RNA-seq analysis showed that multiple pathways and targets were involved in this process,with the anti-inflammatory pathway as the most significant.This study has shown for the first time that mfat-1 has protective effects on HIBD in mice.Activation of a G protein-coupled receptor 120(GPR120)-related anti-inflammatory pathway may be associated with perioperative and postoperative complications,thus innovating clinical intervention strategy may potentially benefit patients with HIBD.展开更多
Through investigating the effect of mild hypothermia on activity of nitric oxide snythase (NOS) in cortical neurons and glycemia levels of neonatal rats with hypoxic ischemic brain damage (HIBD). We studied the mechan...Through investigating the effect of mild hypothermia on activity of nitric oxide snythase (NOS) in cortical neurons and glycemia levels of neonatal rats with hypoxic ischemic brain damage (HIBD). We studied the mechanism of protecting hypoxic ischemic neurons of mild hypothermia. We established neonatal rat HIBD models, used NOS immunohistochemistry and glycemia determination by micromethod. The number of cortical NOS positive neurons after hypoxic ischemia was significantly decreased as compared with controls. The glycemia levels was significantly increased than that controls. No significant difference was found in number of cortical NOS positive neurons and glycemia levels between 31℃ and 34℃ mild hypothemia. The results imply that hypothermia can decrease overproduction of NO through inhibiting the increase of the activity of NOS, and increase the glycemia levels, thus protect the hypoxic ischemic neurons.展开更多
Objective:To investigate the predictive value of of serum NSE,umbilical cord blood albumin levels in hyperbilirubinemia full-term neonates with brain injury.Methods:300 cases of hyperbilirubinemia full-term neonates i...Objective:To investigate the predictive value of of serum NSE,umbilical cord blood albumin levels in hyperbilirubinemia full-term neonates with brain injury.Methods:300 cases of hyperbilirubinemia full-term neonates in our hospital during January 2018 to November 2019 were chosen as hyperbilirubinemia group,200 cases of healthy full-term neonates who were delivered in our hospital during the same period and whose general information matched were chosen as normal control group.According to whether the hyperbilirubinemia group had brain injury,they were further divided into bilirubin encephalopathy group(n=34)and non-bilirubin encephalopathy group(n=266).NSE,umbilical cord blood albumin levels in hyperbilirubinemia group and normal control group were compared.Clinical data,NSE and umbilical cord blood albumin levels between bilirubin encephalopathy group,non-bilirubin encephalopathy group were compared.Risk factors associated with brain injury in full-term newborn with hyperbilirubinemia were analyzed by logistics regression,predictive value of NSE and umbilical cord blood albumin on brain injury in full-term newborn with hyperbilirubinemia were evaluated by ROC curve.Results:NSE level in hyperbilirubinemia group was higher than that in normal control group(P<0.05).There was no significant difference in umbilical cord blood albumin between two groups(P>0.05).Incidence of jaundice,anemia,indirect bilirubin peak,total bilirubin peak and NSE level in bilirubin encephalopathy group were higher than those in non-bilirubin encephalopathy group,level of umbilical cord blood albumin was lower than that in non-bilirubin encephalopathy group(P<0.05).Logistic regression analysis showed that jaundice,anemia,indirect bilirubin peak,total bilirubin peak,NSE and umbilical cord blood albumin within 24h after birth were risk factors for hyperbilirubinemia with brain injury(P<0.05).When NSE was 67.09 ng/mL,the yoden index was the highest,with sensitivity and specificity of 79.70%,55.88%respectively.When the umbilical cord blood albumin was 4.20mg/mL,the jorden index was the highest,sensitivity and specificity were 76.32%,82.35%respectively.Conclusion:Abnormal changes in serum NSE,umbilical cord blood albumin levels are observed in full-term neonates with hyperbilirubinemia,moreover they have value of early prediction for subsequent brain injury.展开更多
The main features of early rehabilitation after severe brain damage are discussed in the article. The most important component for the entire rehabilitation process and the subsequent life of the patient is considered...The main features of early rehabilitation after severe brain damage are discussed in the article. The most important component for the entire rehabilitation process and the subsequent life of the patient is considered restoration of consciousness. Team seems to be a key factor in regaining consciousness along with the restoration of vital functions, movement, cognition, and behavior in these patients. The basic working principle is feedback to any minimal movement, or vegetative signal of a patient, beyond specific professional targets. A network of feedbacks with a patient and between professionals, that is, free flow of information, can be built only through work in a transdisciplinary team mode. The net of feedbacks with the patient and inter-professional ones builds up the team as Non-linear Complex System. Characteristics of “Team-Patient” system status are energy, entropy, and complexity. Teamwork techniques are individualized for resulting optimization of system condition. Increase of complexity is a powerful tool for propulsion of recovery process. Then consciousness may appear as a result of system self-organization. The article reflects the authors’ view on interdisciplinary studies of the phenomenon of consciousness through its impairment and recovery. It focuses on the work of the “proper rehabilitation team”, the mechanisms of its action and methods for researching the occurring phenomena.展开更多
Introduction: Subclinical brain damage in essential hypertension is more prevalent than cardiovascular or renal impairment;nevertheless, screening for nervous system involvement is difficult due to the low accessibili...Introduction: Subclinical brain damage in essential hypertension is more prevalent than cardiovascular or renal impairment;nevertheless, screening for nervous system involvement is difficult due to the low accessibility and high costs of these techniques. Objective: To assess the frequency of silent target organ damage in a cohort of asymptomatic hypertensive patients and to evaluate the potential usefulness of carotid ultrasonographic (US) variables as predictors of subclinical brain damage. Patients and Methods: Thirty four neurologically asymptomatic subjects (mean age 59 years) with essential hypertension were included. Target organ damage was evaluated: degree of hypertensive retinopathy, heart, kidney and brain. Structural and hemodynamical carotid Doppler US parameters were also investigated. Results: The brain was the most frequently affected target organ (70.6%), followed by the heart (67.9%) and kidney (58.6%). Carotid US parameters showed no association of intima media thickness with brain MRI results;nevertheless, decreased diastolic flow velocity and increased resistive index pointed to a resistive carotid flow pattern in patients with classical brain MRI lesions and predicted subclinical lesions with a sensitivity of 70% and 74% and a specificity of 72% and 80% respectively. Conclusions: This study supports previous findings that place the brain as the most frequently affected target organ in essential hypertensive patients and sheds more light on the potential usefulness of carotid structure and hemodynamics as imaging biomarkers of subclinical brain lesions.展开更多
MicroRNAs(miRNAs)play an important regulatory role in neuronal growth and development.Different mi RNAs target different genes to protect neurons in different ways,such as by avoiding apoptosis,preventing degeneration...MicroRNAs(miRNAs)play an important regulatory role in neuronal growth and development.Different mi RNAs target different genes to protect neurons in different ways,such as by avoiding apoptosis,preventing degeneration mediated by conditional mediators,preventing neuronal loss,weakening certain neurotoxic mechanisms,avoiding damage to neurons,and reducing inflammatory damage to them.The high expression of mi RNAs in the brain has significantly facilitated their development as protective targets for therapy,including neuroprotection and neuronal recovery.mi RNA is indispensable to the growth and development of neurons,and in turn,is beneficial for the development of the brain and checking the progression of various diseases of the nervous system.It can thus be used as an important therapeutic target for models of various diseases.This review provides an introduction to the protective effects of mi RNA on neurons in case of different diseases or damage models,and then provides reference values and reflections on the relevant treatments for the benefit of future research in the area.展开更多
BACKGROUND Cerebral apoplexy patients are prone to cognitive impairment,and it is very important to choose appropriate treatment methods to improve their cognitive impairment after stroke.AIM To evaluate the effects o...BACKGROUND Cerebral apoplexy patients are prone to cognitive impairment,and it is very important to choose appropriate treatment methods to improve their cognitive impairment after stroke.AIM To evaluate the effects of enhanced external counterpulsation(EECP)in con-junction with atorvastatin on cognitive function,neurotransmitter levels,and the repair of brain tissue damage in patients with cognitive impairment due to stroke.METHODS In this retrospective study,data from 60 patients with poststroke cognitive impairment due to stroke who were treated in our hospital from February 2021 to July 2022 were analyzed and divided into a treatment group(n=30)and a control group(n=30)according to the different nursing methods applied.Patients in the treatment group received EECP in addition to atorvastatin,while those in the control group received atorvastatin alone.Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA)and activities of daily living(ADL)scale scores were compared between the two groups.Additionally,the two groups were compared in terms of serum acetylcholine(ACh),acetylcholin-esterase(AChE),nitric oxide(NO),endothelin-1(ET-1),β2-microglobulin(β2-MG),glial fibrillary acidic protein(GFAP),and visinin-like protein 1(VILIP-1)in the serum.Blood flow measurements from the anterior cerebral artery(ACA),middle cerebral artery(MCA)and posterior cerebral artery(PCA)were compared between the two groups before and after treatment,and the pulsatility index(PI)and resistance index(RI)of each artery were determined.RESULTS MMSE,MoCA,and ADL scores all improved in both groups following treatment,with the study group showing more improvement than the control group(P<0.05).After treatment,there were statistically significant increases in both ACh and NO levels,whereas decreases occurred in AChE,ET-1,β2-MG,VILIP-1,and GFAP,levels and the PI and RI of the left-ACA,right-ACA,left-MCA,right-MCA,left-PCA,and right-PCA.The study group showed greater gains in all metrics than the control group(P<0.05).CONCLUSION EECP combined with atorvastatin is effective in the treatment of cognitive impairment after stroke and can effectively improve the cognitive function,neurotransmitter levels,and brain tissue damage status of patients.展开更多
Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic ...Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.展开更多
One of the major challenges in emergency medicine is out-of-hospital cardiac arrest(OHCA).Every year,about 53–62/100000 people worldwide suffer an out-of-hospital cardiac arrest with serious consequences,whereas pers...One of the major challenges in emergency medicine is out-of-hospital cardiac arrest(OHCA).Every year,about 53–62/100000 people worldwide suffer an out-of-hospital cardiac arrest with serious consequences,whereas persistent brain injury is a major cause of morbidity and mortality of those surviving a cardiac arrest.Today,only few and insufficient strategies are known to limit neurological damage of ischemia and reperfusion injury.The aim of the present study was to investigate whether teriflunomide,an approved drug for treatment of relapsing-remitting-multiple-sclerosis,exerts a protective effect on brain cells in an in vitro model of ischemia.Therefore,organotypic slice cultures from rat hippocampus and cerebellum were exposed to oxygen-glucose-deprivation and subsequently treated with teriflunomide.The administration of teriflunomide in the reperfusion time on both hippocampal and cerebellar slice cultures significantly decreased the amount of detectable propidium iodide signal compared with an untreated culture,indicating that more cells survive after oxygen-glucosedeprivation.However,hippocampal slice cultures showed a higher vulnerability to ischemic conditions and a more sensitive response to teriflunomide compared with cerebellar slice cultures.Our study suggests that teriflunomide,applied as a post-treatment after an oxygenglucose-deprivation,has a protective effect on hippocampal and cerebellar cells in organotypic slice cultures of rats.All procedures were conducted under established standards of the German federal state of North Rhine Westphalia,in accordance with the European Communities Council Directive 2010/63/EU on the protection of animals used for scientific purposes.展开更多
Objective: To investigate the effect of Cannabis sativa extract on the development of neuroand hepato-toxicity caused by malathion injection in rats. Methods: The extract of Cannabis sativa was obtained from the plant...Objective: To investigate the effect of Cannabis sativa extract on the development of neuroand hepato-toxicity caused by malathion injection in rats. Methods: The extract of Cannabis sativa was obtained from the plant resin by chloroform treatment. Δ~9-Tetrahydrocannabinol content of the extract(20%) was quantified using gas chromatography–mass spectrometry. The doses of cannabis extract were expressed as Δ~9-tetrahydrocannabinol content of 10 or 20 mg/kg. Malathion(150 mg/kg) was intraperitoneally administered followed after 30 min by the cannabis extract(10 or 20 mg/kg, subcutaneously). Rats were euthanized 4 h later. Malondialdehyde(MDA), reduced glutathione(GSH), nitric oxide and paraoxonase-1(PON-1) activity were determined in brain and liver. Brain 5-lipoxygenase and butyrylcholinesterase(BChE) activity were measured as well. Histopathological examination of brain and liver tissue was also performed. Results: Compared to controls, malathion resulted in increased oxidative stress in brain and liver. MDA and nitric oxide concentrations were significantly increased(P<0.05) and GSH significantly decreased with respect to control levels(P<0.05). Malathion also significantly inhibited PON-1 and BChE activities but had no effect on brain 5-lipoxygenase. Brain MDA concentrations were not altered by cannabis treatment. Cannabis at 20 mg/kg, however, caused significant increase in nitric oxide and restored the GSH and PON-1 activity. Brain BChE activity significantly decreased by 26.1%(P<0.05) after treatment with 10 mg/kg cannabis. Cannabis showed no effect on brain 5-lipoxygenase. On the other hand, rats treated with cannabis exhibited significantly higher levels of liver MDA, nitric oxide and PON-1 activity compared with the malathion control group. Rats treated with only malathion exhibited spongiform changes, neuronal damage in the cerebral cortex and degeneration of some Purkinje cells in the cerebellum. There were also hepatic vacuolar degeneration and dilated and congested portal vein. These histopthological changes induced by malathion in brain and liver were reduced to great extent by cannabis administration at 20 mg/kg. Conclusions: Our data suggest that acute treatment with cannabis alleviates the malathion-induced brain and hepatic injury in rats possibly by maintaining the levels of GSH and PON-1 activity.展开更多
The binding properties of neural cell adhesion molecule are modulated by a polysialic acid moiety. This plays an important role in the migration of adult born neuroblasts from their area of origin, the subventricular ...The binding properties of neural cell adhesion molecule are modulated by a polysialic acid moiety. This plays an important role in the migration of adult born neuroblasts from their area of origin, the subventricular zone, towards the olfactory bulb. Polysialisation increases the migration speed of the cells and helps to prevent the neuroblasts from leaving their migration route, the rostral migratory stream. Here, we evaluated the potential of intraventricular application of endoneuraminidase-N, an enzyme that specifically cleaves polysialic acid from neural cell adhesion molecule, in a rat model for structural prefrontal cortex damage. As expected, endoneuraminidase-N caused the rostral migratory stream to become wider, with a less uniform cellular orientation. Furthermore, endoneuraminidase-N treatment caused the neuroblasts to leave the rostral migratory stream and migrate towards the lesioned tissue. Despite the neuroblasts not being differentiated into neurons after a survival time of three weeks, this technique provides a solid animal model for future work on the migration and differentiation of relocated neuroblasts and might provide a basis for a future endogenous stem cell-based therapy for structural brain damage. The experiments were approved by the local animal care committee(522-27-11/02-00, 115;Senatorin für Wissenschaft, Gesundheit und Verbraucherschutz, Bremen, Germany) on February 10, 2016.展开更多
BACKGROUND There are very few studies on the differential diagnosis between egocentric neglect(EN)and allocentric neglect(AN).AIM To investigate the overall trend of the previously developed assessment tools by conduc...BACKGROUND There are very few studies on the differential diagnosis between egocentric neglect(EN)and allocentric neglect(AN).AIM To investigate the overall trend of the previously developed assessment tools by conducting a descriptive review of the studies on assessment tools that can perform a differential diagnosis of EN and AN.METHODS The data were collected by using databases such as Google Scholar,PubMed,and ScienceDirect.The most commonly used search terms were“neglect”,“stroke”,“egocentric neglect”,and“allocentric neglect”.RESULTS A total of seven studies that met the inclusion criteria were selected and analyzed.We were able to confirm the research process,test method,and differential diagnosis criteria of the seven presented assessment tools from four studies on paper-based tests and three studies on computerized tests.The majority of the tests were carried out via the cancellation method using stimuli such as everyday objects or numbers.EN distinguished the left from right based on the test paper,while AN distinguished the left from right based on stimuli.In order to perform differential diagnosis,the difference in the number of left and right responses or non-responses was used based on the EN and AN criteria.CONCLUSION It was confirmed that all the seven assessment tools can effectively perform differential diagnosis of EN and AN.This study may provide important data that can be used in clinical practice for differential diagnosis and future intervention planning for neglect patients.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;">Recovering from multiple traumatic brain injury (TBI) is a very difficult task, depending on the severity of the les...<div style="text-align:justify;"> <span style="font-family:Verdana;">Recovering from multiple traumatic brain injury (TBI) is a very difficult task, depending on the severity of the lesions, the affected parts of the brain and the level of damage (locomotor, cognitive or sensory). Although there are some software platforms to help these patients to recover part of the lost capacity, the variety of existing lesions and the different degree to which they affect the patient, do not allow the generalization of the appropriate treatments and tools in each case. The aim of this work is to design and evaluate a machine vision-based UI (User Interface) allowing patients with a high level of injury to interact with a computer. This UI will be a tool for the therapy they follow and a way to communicate with their environment. The interface provides a set of specific activities, developed in collaboration with the multidisciplinary team that is currently evaluating each patient, to be used as a part of the therapy they receive. The system has been successfully tested with two patients whose degree of disability prevents them from using other types of platforms.</span> </div>展开更多
文摘Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated with specific central nervous system zones or areas, and its prognosis is uncertain. This case study describes a 62-year-old male patient with acquired brain damage of the anterior cingulate cortex as a result of an ischemic event in the territory of the left anterior cerebral artery. Cognitive function was assessed using the neuropsychological executive function and frontal lobe test battery (BANFE-2) as well as other neuropsychological tests. The results show a profile of higher mental functions characterized by the presence of dysexecutive syndrome with marked behavioral alteration and diencephalic amnesia. .
基金financially supported by the National Natural Science Foundation of China,No.81771625(to XF)the Jiangsu Provincial Key Medical Discipline of China,No.ZDXKA2016013(to XF)the Pediatric Clinical Center of Suzhou City of China,No.Szzx201504(to XF)
文摘Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.
基金supported by the National Natural Science Foundation of China,Nos.81872845(to ML),81771625(to XF)the Natural Science Foundation of Jiangsu Province of China,No.BK20180207(to ML)+4 种基金Jiangsu Provincial Medical Youth Talent of China,No.QNRC2016762(to ML)the Pediatric Clinical Center of Suzhou City of China,No.Szzx201504(to XF)Postgraduate Research&Practice Innovation Program of Jiangsu Province of China,No.KYCX19_1998(to LLT)Jiangsu Government Scholarship for Overseas Studies of China,No.JS-2017-127(to ML)the Fifth Batch of Gusu Health Talent Plan of China(to ML).
文摘Our previous studies have demonstrated that TP53-induced glycolysis and apoptosis regulator(TIGAR)can protect neurons after cerebral ischemia/reperfusion.However,the role of TIGAR in neonatal hypoxic-ischemic brain damage(HIBD)remains unknown.In the present study,7-day-old Sprague-Dawley rat models of HIBD were established by permanent occlusion of the left common carotid artery followed by 2-hour hypoxia.At 6 days before induction of HIBD,a lentiviral vector containing short hairpin RNA of either TIGAR or gasdermin D(LV-sh_TIGAR or LV-sh_GSDMD)was injected into the left lateral ventricle and striatum.Highly aggressively proliferating immortalized(HAPI)microglial cell models of in vitro HIBD were established by 2-hour oxygen/glucose deprivation followed by 24-hour reoxygenation.Three days before in vitro HIBD induction,HAPI microglial cells were transfected with LV-sh_TIGAR or LV-sh_GSDMD.Our results showed that TIGAR expression was increased in the neonatal rat cortex after HIBD and in HAPI microglial cells after oxygen/glucose deprivation/reoxygenation.Lentivirusmediated TIGAR knockdown in rats markedly worsened pyroptosis and brain damage after hypoxia/ischemia in vivo and in vitro.Application of exogenous nicotinamide adenine dinucleotide phosphate(NADPH)increased the NADPH level and the glutathione/oxidized glutathione ratio and decreased reactive oxygen species levels in HAPI microglial cells after oxygen/glucose deprivation/reoxygenation.Additionally,exogenous NADPH blocked the effects of TIGAR knockdown in neonatal HIBD in vivo and in vitro.These findings show that TIGAR can inhibit microglial pyroptosis and play a protective role in neonatal HIBD.The study was approved by the Animal Ethics Committee of Soochow University of China(approval No.2017LW003)in 2017.
基金supported by the National Natural Science Foundation of China,No.81070523 and 81270728
文摘Neural stem/progenitor cell(NSC) transplantation has been shown to effectively improve neurological function in rats with hypoxic-ischemic brain damage.Vascular endothelial growth factor(VEGF) is a signaling protein that stimulates angiogenesis and improves neural regeneration.We hypothesized that transplantation of VEGF-transfected NSCs would alleviate hypoxic-ischemic brain damage in neonatal rats.We produced and transfected a recombinant lentiviral vector containing the VEGF165 gene into cultured NSCs.The transfected NSCs were transplanted into the left sensorimotor cortex of rats 3 days after hypoxic-ischemic brain damage.Compared with the NSCs group,VEGF m RNA and protein expression levels were increased in the transgene NSCs group,and learning and memory abilities were significantly improved at 30 days.Furthermore,histopathological changes were alleviated in these animals.Our findings indicate that transplantation of VEGF-transfected NSCs may facilitate the recovery of neurological function,and that its therapeutic effectiveness is better than that of unmodified NSCs.
基金This study was supported by the National Natural Science Foundation of China,Nos.81871193(to XD),81671532(to BS),81771625&81701490(to XF),81801505(to MG)Jiangsu Provincial Medical Youth Talent of China,Nos.QNRC2016763(to XD),QNRC2016758(to LXX),QNRC2016762(to ML)+7 种基金the Science and Technology Project of Suzhou City of China,No.SS201709(to XD)the Natural Science Foundation of Jiangsu Province of China,No.BK20180205(to XD)the Training Program Foundation for Health Talents of Gusu of China,No.GSWS2019049(to XD)the Jiangsu Provincial Key Medical Discipline of China,No.ZDXKA2016013(to XF)the Jiangsu Province Women and Children Health Research Project of China,No.F201750(to LXX)the Pediatric Clinical Center of Suzhou City of China,No.Szzx201504(to XF)Suzhou Industrial Technology Innovation Project of China,No.SYS201765(to LZ)the Project of Suzhou Science,Education and Health and Technology,China,No.KJXW2018018(to ML).
文摘Circadian rhythm disorder is a common,but often neglected,consequence of neonatal hypoxic-ischemic brain damage(HIBD).However,the underlying molecular mechanisms remain largely unknown.We previously showed that,in a rat model of HIBD,up-regulation of microRNA-325(miR-325)in the pineal gland is responsible for the suppression of Aanat,a key enzyme involved in melatonin synthesis and circadian rhythm regulation.To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD,we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University(Dushuhu Branch)in 2019.We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD.Furthermore,a luciferase reporter gene assay revealed that LIM homeobox 3(LHX3)is a novel downstream target of miR-325.In addition,in miR-325 knock-down mice,the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland.We established a neonatal mouse model of HIBD by performing doublelayer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours.Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions.Finally,we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3.Taken together,our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD.The clinical trial was approved by Institutional Review Board of Children’s Hospital of Soochow University(approval No.2015028)on July 20,2015.Animal experiments were approved by Animal Care and Use Committee,School of Medicine,Soochow University,China(approval No.XD-2016-1)on January 15,2016.
基金the Scientific Research Program of Health Bureau of Chongqing City, No. [2007]1-07-2-153
文摘BACKGROUND: Central nervous system axons regenerate poorly following neonatal hypoxic-ischemic brain damage (HIBD), partly due to inhibitors, such as Nogo-A. Very few studies have addressed the regulation of Nogo-A in neonatal rats following HIBD. However, numerous studies have shown that ephedrine accelerates neuronal remodeling and promotes recovery of neural function in neonatal rats following HIBD. OBJECTIVE: To investigate the effects of ephedrine on expression of Nogo-A and synaptophysin in brain tissues of neonatal rats following HIBD. DESIGN, TIME AND SETTING: A completely randomized, controlled study was performed at the Immunohistochemistry Laboratory of the Research Institute of Pediatrics, Children's Hospital of Chongqing Medical University from August 2008 to March 2009. MATERIALS: Ephedrine hydrochloride (Chifeng Pharmaceutical Group, China), rabbit anti-Nogo-A polyclonal antibody (Abcam, UK), and rabbit antisynaptophysin polyclonal antibody (Lab Vision, USA) were used in this study. METHODS: A total of 96 healthy, neonatal, Sprague Dawley rats were randomly assigned to three groups (n = 32): sham operation, HIBD, and ephedrine. The HIBD model was established by permanent occlusion of the left common carotid artery, followed by 2 hours of hypoxia (8% oxygen and 92% nitrogen). In the sham operation group, the left common carotid artery was exposed, but was not ligated or subjected to hypoxia. Rats in the ephedrine group were intraperitoneally injected with ephedrine immediately following HIBD, with 1.5 mg/kg each time. Rats in the sham operation and HIBD groups were injected with an equal volume of saline. All neonatal rats were treated once daily for 7 days. MAIN OUTCOME MEASURES: Histopathological damage to the cortex and hippocampus was determined by hematoxylin-eosin staining. Expression of Nogo-A and synaptophysin was detected using immunohistochemical staining. RESULTS: Neuronal degeneration and edema were observed in the hypoxic-ischemic cortex and hippocampus by hematoxylin-eosin staining. Compared with the sham operation group, the levels of Nogo-A significantly increased in the HIBD group at various time points (P < 0.01). Nogo-A expression was significantly reduced in the ephedrine group compared with the HIBD group (P < 0.01). Synaptophysin expression was significantly decreased in the hypoxic-ischemic cortex, compared with the sham operation group (P < 0.01). Synaptophysin levels were significantly increased in the ephedrine group, compared with the HIBD group (P < 0.01). CONCLUSION: Altered Nogo-A expression was associated with inversely altered synaptophysin expression. The use of ephedrine normalized expression levels of Nogo-A and synaptophysin following HIBD.
基金Special Topic of Scientific and Technological Re-search of Traditional ChineseMedicine of the State Adminis-tration of Traditional ChineseMedicine, No. 04-05JL13 theNational Natural Science Foun-dation of China, No.30371812
文摘OBJECTIVE: To investigate the effect of endothelial cells on the permeability of blood brain barrier (BBB) after brain injury and its effect mechanism. DATA SOURCES: We searched for the articles of permeability of BBB and endothelial cell injury after brain ischemia, which were published between January 1982 and December 2005, with the key words of “cerebral ischemia damage,blood brain barrier ( BBB),permeability,effect of endothelial cell (EC) and its variation mechanism”in English. STUDY SELECTION: The materials were primarily selected. The articles related to the changes in the permeability of BBB and the effect of endothelial cells as well as the change mechanism after cerebral ischemia damage were chosen. Repetitive studies or review articles were excluded. DATA EXTRACTION: Totally 55 related articles were collected, and 35 were excluded due to repetitive or review articles, finally 20 articles were involved. DATA SYNTHESIS: The content or viewpoints of involved literatures were analyzed. Cerebral ischemia had damage for endothelial cells, such as the inflow of a lot of Ca2+, the production of nitrogen monoxide and oxygen free radical, and aggravated destruction of BBB. After acceptors of inflammatory mediators on cerebrovascular endothelial cell membrane, such as histamine, bradykinin , 5-hydroxytryptamine and so on are activated, endothelial cells shrink and the permeability of BBB increases. Its mechanism involves in the inflow of extracellular Ca2+and the release of intracellular Ca2+ in the cells. Glycocalyx molecule on the surface of endothelial cell, having structural polytropy, is the determinative factor of the permeability of BBB. VEGF, intensively increasing the vasopermeability and mainly effecting on postcapillary vein and veinlet, is the strongest known blood vessel permeation reagent. Its chronic overexpression in the brain can lead the destruction of BBB. CONCLUSION: The injury of endothelial cell participants in the pathological mechanism of BBB destruction after cerebral ischemia.
基金supported by funds from the National Natural Science Foundation of China(Grant No.31701283 and No.81970164)the National Key R&D Program of China(Grant No.2017YFC1103701 and No.2017YFC1103702)Jiangsu Key Laboratory of Xenotransplantation(Grant No.BM2012116).
文摘Acute hypoxic-ischemic brain damage(HIBD)mainly occurs in adults as a result of perioperative cardiac arrest and asphyxia.The benefits of n-3 polyunsaturated fatty acids(n-3 PUFAs)in maintaining brain growth and development are well documented.However,possible protective targets and underlying mechanisms of mfat-1 mice on HIBD require further investigation.The mfat-1 transgenic mice exhibited protective effects on HIBD,as indicated by reduced infarct range and improved neurobehavioral defects.RNA-seq analysis showed that multiple pathways and targets were involved in this process,with the anti-inflammatory pathway as the most significant.This study has shown for the first time that mfat-1 has protective effects on HIBD in mice.Activation of a G protein-coupled receptor 120(GPR120)-related anti-inflammatory pathway may be associated with perioperative and postoperative complications,thus innovating clinical intervention strategy may potentially benefit patients with HIBD.
文摘Through investigating the effect of mild hypothermia on activity of nitric oxide snythase (NOS) in cortical neurons and glycemia levels of neonatal rats with hypoxic ischemic brain damage (HIBD). We studied the mechanism of protecting hypoxic ischemic neurons of mild hypothermia. We established neonatal rat HIBD models, used NOS immunohistochemistry and glycemia determination by micromethod. The number of cortical NOS positive neurons after hypoxic ischemia was significantly decreased as compared with controls. The glycemia levels was significantly increased than that controls. No significant difference was found in number of cortical NOS positive neurons and glycemia levels between 31℃ and 34℃ mild hypothemia. The results imply that hypothermia can decrease overproduction of NO through inhibiting the increase of the activity of NOS, and increase the glycemia levels, thus protect the hypoxic ischemic neurons.
基金Guilin Scientific Research and Technology Development Project(No.20150403-6-1)Project to improve the basic scientific research ability of young and middle-aged teachers in Guangxi Universities(No.KY2016LX247)Young and middle-aged faculty research capacity Enhancement project of Guilin Medical College(No.2018glmcy096)
文摘Objective:To investigate the predictive value of of serum NSE,umbilical cord blood albumin levels in hyperbilirubinemia full-term neonates with brain injury.Methods:300 cases of hyperbilirubinemia full-term neonates in our hospital during January 2018 to November 2019 were chosen as hyperbilirubinemia group,200 cases of healthy full-term neonates who were delivered in our hospital during the same period and whose general information matched were chosen as normal control group.According to whether the hyperbilirubinemia group had brain injury,they were further divided into bilirubin encephalopathy group(n=34)and non-bilirubin encephalopathy group(n=266).NSE,umbilical cord blood albumin levels in hyperbilirubinemia group and normal control group were compared.Clinical data,NSE and umbilical cord blood albumin levels between bilirubin encephalopathy group,non-bilirubin encephalopathy group were compared.Risk factors associated with brain injury in full-term newborn with hyperbilirubinemia were analyzed by logistics regression,predictive value of NSE and umbilical cord blood albumin on brain injury in full-term newborn with hyperbilirubinemia were evaluated by ROC curve.Results:NSE level in hyperbilirubinemia group was higher than that in normal control group(P<0.05).There was no significant difference in umbilical cord blood albumin between two groups(P>0.05).Incidence of jaundice,anemia,indirect bilirubin peak,total bilirubin peak and NSE level in bilirubin encephalopathy group were higher than those in non-bilirubin encephalopathy group,level of umbilical cord blood albumin was lower than that in non-bilirubin encephalopathy group(P<0.05).Logistic regression analysis showed that jaundice,anemia,indirect bilirubin peak,total bilirubin peak,NSE and umbilical cord blood albumin within 24h after birth were risk factors for hyperbilirubinemia with brain injury(P<0.05).When NSE was 67.09 ng/mL,the yoden index was the highest,with sensitivity and specificity of 79.70%,55.88%respectively.When the umbilical cord blood albumin was 4.20mg/mL,the jorden index was the highest,sensitivity and specificity were 76.32%,82.35%respectively.Conclusion:Abnormal changes in serum NSE,umbilical cord blood albumin levels are observed in full-term neonates with hyperbilirubinemia,moreover they have value of early prediction for subsequent brain injury.
文摘The main features of early rehabilitation after severe brain damage are discussed in the article. The most important component for the entire rehabilitation process and the subsequent life of the patient is considered restoration of consciousness. Team seems to be a key factor in regaining consciousness along with the restoration of vital functions, movement, cognition, and behavior in these patients. The basic working principle is feedback to any minimal movement, or vegetative signal of a patient, beyond specific professional targets. A network of feedbacks with a patient and between professionals, that is, free flow of information, can be built only through work in a transdisciplinary team mode. The net of feedbacks with the patient and inter-professional ones builds up the team as Non-linear Complex System. Characteristics of “Team-Patient” system status are energy, entropy, and complexity. Teamwork techniques are individualized for resulting optimization of system condition. Increase of complexity is a powerful tool for propulsion of recovery process. Then consciousness may appear as a result of system self-organization. The article reflects the authors’ view on interdisciplinary studies of the phenomenon of consciousness through its impairment and recovery. It focuses on the work of the “proper rehabilitation team”, the mechanisms of its action and methods for researching the occurring phenomena.
文摘Introduction: Subclinical brain damage in essential hypertension is more prevalent than cardiovascular or renal impairment;nevertheless, screening for nervous system involvement is difficult due to the low accessibility and high costs of these techniques. Objective: To assess the frequency of silent target organ damage in a cohort of asymptomatic hypertensive patients and to evaluate the potential usefulness of carotid ultrasonographic (US) variables as predictors of subclinical brain damage. Patients and Methods: Thirty four neurologically asymptomatic subjects (mean age 59 years) with essential hypertension were included. Target organ damage was evaluated: degree of hypertensive retinopathy, heart, kidney and brain. Structural and hemodynamical carotid Doppler US parameters were also investigated. Results: The brain was the most frequently affected target organ (70.6%), followed by the heart (67.9%) and kidney (58.6%). Carotid US parameters showed no association of intima media thickness with brain MRI results;nevertheless, decreased diastolic flow velocity and increased resistive index pointed to a resistive carotid flow pattern in patients with classical brain MRI lesions and predicted subclinical lesions with a sensitivity of 70% and 74% and a specificity of 72% and 80% respectively. Conclusions: This study supports previous findings that place the brain as the most frequently affected target organ in essential hypertensive patients and sheds more light on the potential usefulness of carotid structure and hemodynamics as imaging biomarkers of subclinical brain lesions.
基金supported by the National Natural Science Foundation of China,No.81801208(to LSO)Science and Technology Program of Guangzhou,No.202102080053(to YF)+1 种基金Science and Technology Program of Guangzhou,No.202007030001(to YMT)Science and Technology Planning Project of Guangzhou,No.202102020027(to ZL)。
文摘MicroRNAs(miRNAs)play an important regulatory role in neuronal growth and development.Different mi RNAs target different genes to protect neurons in different ways,such as by avoiding apoptosis,preventing degeneration mediated by conditional mediators,preventing neuronal loss,weakening certain neurotoxic mechanisms,avoiding damage to neurons,and reducing inflammatory damage to them.The high expression of mi RNAs in the brain has significantly facilitated their development as protective targets for therapy,including neuroprotection and neuronal recovery.mi RNA is indispensable to the growth and development of neurons,and in turn,is beneficial for the development of the brain and checking the progression of various diseases of the nervous system.It can thus be used as an important therapeutic target for models of various diseases.This review provides an introduction to the protective effects of mi RNA on neurons in case of different diseases or damage models,and then provides reference values and reflections on the relevant treatments for the benefit of future research in the area.
基金This study was approved by the Ethics Committee of Shengjing Hospital of China Medical University.
文摘BACKGROUND Cerebral apoplexy patients are prone to cognitive impairment,and it is very important to choose appropriate treatment methods to improve their cognitive impairment after stroke.AIM To evaluate the effects of enhanced external counterpulsation(EECP)in con-junction with atorvastatin on cognitive function,neurotransmitter levels,and the repair of brain tissue damage in patients with cognitive impairment due to stroke.METHODS In this retrospective study,data from 60 patients with poststroke cognitive impairment due to stroke who were treated in our hospital from February 2021 to July 2022 were analyzed and divided into a treatment group(n=30)and a control group(n=30)according to the different nursing methods applied.Patients in the treatment group received EECP in addition to atorvastatin,while those in the control group received atorvastatin alone.Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA)and activities of daily living(ADL)scale scores were compared between the two groups.Additionally,the two groups were compared in terms of serum acetylcholine(ACh),acetylcholin-esterase(AChE),nitric oxide(NO),endothelin-1(ET-1),β2-microglobulin(β2-MG),glial fibrillary acidic protein(GFAP),and visinin-like protein 1(VILIP-1)in the serum.Blood flow measurements from the anterior cerebral artery(ACA),middle cerebral artery(MCA)and posterior cerebral artery(PCA)were compared between the two groups before and after treatment,and the pulsatility index(PI)and resistance index(RI)of each artery were determined.RESULTS MMSE,MoCA,and ADL scores all improved in both groups following treatment,with the study group showing more improvement than the control group(P<0.05).After treatment,there were statistically significant increases in both ACh and NO levels,whereas decreases occurred in AChE,ET-1,β2-MG,VILIP-1,and GFAP,levels and the PI and RI of the left-ACA,right-ACA,left-MCA,right-MCA,left-PCA,and right-PCA.The study group showed greater gains in all metrics than the control group(P<0.05).CONCLUSION EECP combined with atorvastatin is effective in the treatment of cognitive impairment after stroke and can effectively improve the cognitive function,neurotransmitter levels,and brain tissue damage status of patients.
基金supported by the National Natural Science Foundation of China,Nos.82301486(to SL)and 82071325(to FY)Medjaden Academy&Research Foundation for Young Scientists,No.MJR202310040(to SL)+2 种基金Nanjing Medical University Science and Technique Development Foundation Project,No.NMUB20220060(to SL)Medical Scientific Research Project of Jiangsu Commission of Health,No.ZDA2020019(to JZ)and Health China Buchang Zhiyuan Public Welfare Project for Heart and Brain Health,No.HIGHER202102(to QD).
文摘Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.
文摘One of the major challenges in emergency medicine is out-of-hospital cardiac arrest(OHCA).Every year,about 53–62/100000 people worldwide suffer an out-of-hospital cardiac arrest with serious consequences,whereas persistent brain injury is a major cause of morbidity and mortality of those surviving a cardiac arrest.Today,only few and insufficient strategies are known to limit neurological damage of ischemia and reperfusion injury.The aim of the present study was to investigate whether teriflunomide,an approved drug for treatment of relapsing-remitting-multiple-sclerosis,exerts a protective effect on brain cells in an in vitro model of ischemia.Therefore,organotypic slice cultures from rat hippocampus and cerebellum were exposed to oxygen-glucose-deprivation and subsequently treated with teriflunomide.The administration of teriflunomide in the reperfusion time on both hippocampal and cerebellar slice cultures significantly decreased the amount of detectable propidium iodide signal compared with an untreated culture,indicating that more cells survive after oxygen-glucosedeprivation.However,hippocampal slice cultures showed a higher vulnerability to ischemic conditions and a more sensitive response to teriflunomide compared with cerebellar slice cultures.Our study suggests that teriflunomide,applied as a post-treatment after an oxygenglucose-deprivation,has a protective effect on hippocampal and cerebellar cells in organotypic slice cultures of rats.All procedures were conducted under established standards of the German federal state of North Rhine Westphalia,in accordance with the European Communities Council Directive 2010/63/EU on the protection of animals used for scientific purposes.
文摘Objective: To investigate the effect of Cannabis sativa extract on the development of neuroand hepato-toxicity caused by malathion injection in rats. Methods: The extract of Cannabis sativa was obtained from the plant resin by chloroform treatment. Δ~9-Tetrahydrocannabinol content of the extract(20%) was quantified using gas chromatography–mass spectrometry. The doses of cannabis extract were expressed as Δ~9-tetrahydrocannabinol content of 10 or 20 mg/kg. Malathion(150 mg/kg) was intraperitoneally administered followed after 30 min by the cannabis extract(10 or 20 mg/kg, subcutaneously). Rats were euthanized 4 h later. Malondialdehyde(MDA), reduced glutathione(GSH), nitric oxide and paraoxonase-1(PON-1) activity were determined in brain and liver. Brain 5-lipoxygenase and butyrylcholinesterase(BChE) activity were measured as well. Histopathological examination of brain and liver tissue was also performed. Results: Compared to controls, malathion resulted in increased oxidative stress in brain and liver. MDA and nitric oxide concentrations were significantly increased(P<0.05) and GSH significantly decreased with respect to control levels(P<0.05). Malathion also significantly inhibited PON-1 and BChE activities but had no effect on brain 5-lipoxygenase. Brain MDA concentrations were not altered by cannabis treatment. Cannabis at 20 mg/kg, however, caused significant increase in nitric oxide and restored the GSH and PON-1 activity. Brain BChE activity significantly decreased by 26.1%(P<0.05) after treatment with 10 mg/kg cannabis. Cannabis showed no effect on brain 5-lipoxygenase. On the other hand, rats treated with cannabis exhibited significantly higher levels of liver MDA, nitric oxide and PON-1 activity compared with the malathion control group. Rats treated with only malathion exhibited spongiform changes, neuronal damage in the cerebral cortex and degeneration of some Purkinje cells in the cerebellum. There were also hepatic vacuolar degeneration and dilated and congested portal vein. These histopthological changes induced by malathion in brain and liver were reduced to great extent by cannabis administration at 20 mg/kg. Conclusions: Our data suggest that acute treatment with cannabis alleviates the malathion-induced brain and hepatic injury in rats possibly by maintaining the levels of GSH and PON-1 activity.
文摘The binding properties of neural cell adhesion molecule are modulated by a polysialic acid moiety. This plays an important role in the migration of adult born neuroblasts from their area of origin, the subventricular zone, towards the olfactory bulb. Polysialisation increases the migration speed of the cells and helps to prevent the neuroblasts from leaving their migration route, the rostral migratory stream. Here, we evaluated the potential of intraventricular application of endoneuraminidase-N, an enzyme that specifically cleaves polysialic acid from neural cell adhesion molecule, in a rat model for structural prefrontal cortex damage. As expected, endoneuraminidase-N caused the rostral migratory stream to become wider, with a less uniform cellular orientation. Furthermore, endoneuraminidase-N treatment caused the neuroblasts to leave the rostral migratory stream and migrate towards the lesioned tissue. Despite the neuroblasts not being differentiated into neurons after a survival time of three weeks, this technique provides a solid animal model for future work on the migration and differentiation of relocated neuroblasts and might provide a basis for a future endogenous stem cell-based therapy for structural brain damage. The experiments were approved by the local animal care committee(522-27-11/02-00, 115;Senatorin für Wissenschaft, Gesundheit und Verbraucherschutz, Bremen, Germany) on February 10, 2016.
基金Supported by the National Research Foundation of Korea Grant funded by the Korea government,No.2021R1G1A1093494.
文摘BACKGROUND There are very few studies on the differential diagnosis between egocentric neglect(EN)and allocentric neglect(AN).AIM To investigate the overall trend of the previously developed assessment tools by conducting a descriptive review of the studies on assessment tools that can perform a differential diagnosis of EN and AN.METHODS The data were collected by using databases such as Google Scholar,PubMed,and ScienceDirect.The most commonly used search terms were“neglect”,“stroke”,“egocentric neglect”,and“allocentric neglect”.RESULTS A total of seven studies that met the inclusion criteria were selected and analyzed.We were able to confirm the research process,test method,and differential diagnosis criteria of the seven presented assessment tools from four studies on paper-based tests and three studies on computerized tests.The majority of the tests were carried out via the cancellation method using stimuli such as everyday objects or numbers.EN distinguished the left from right based on the test paper,while AN distinguished the left from right based on stimuli.In order to perform differential diagnosis,the difference in the number of left and right responses or non-responses was used based on the EN and AN criteria.CONCLUSION It was confirmed that all the seven assessment tools can effectively perform differential diagnosis of EN and AN.This study may provide important data that can be used in clinical practice for differential diagnosis and future intervention planning for neglect patients.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;">Recovering from multiple traumatic brain injury (TBI) is a very difficult task, depending on the severity of the lesions, the affected parts of the brain and the level of damage (locomotor, cognitive or sensory). Although there are some software platforms to help these patients to recover part of the lost capacity, the variety of existing lesions and the different degree to which they affect the patient, do not allow the generalization of the appropriate treatments and tools in each case. The aim of this work is to design and evaluate a machine vision-based UI (User Interface) allowing patients with a high level of injury to interact with a computer. This UI will be a tool for the therapy they follow and a way to communicate with their environment. The interface provides a set of specific activities, developed in collaboration with the multidisciplinary team that is currently evaluating each patient, to be used as a part of the therapy they receive. The system has been successfully tested with two patients whose degree of disability prevents them from using other types of platforms.</span> </div>
