Bone marrow mesenchymal stem cells have received great attention in the studies of therapeutic methods of cerebral ischemia in recent years. This article reviews its research Status Quo and some unsolved problems.

5-lipoxygenase-activating protein Gene (ALOX5AP) on chromosome 13q12-13 encodes 5-lipoxygenase-activating protein (FLAP). The latter plays a key role in regulating the synthesis of leukotriene. Studies have suggested that the subjects who carry this gene may increase stroke risk by two times. Therefore, ALOX5AP plays an important role in the pathogenesis of stroke.

Objective To investigate the expression of nuclear factor kappa B (NF-?B ) in focal cerebral ischemia and reperfusion and effects of N-acetylcysteine (NAC) pretreatment.Methods The focal cerebral ischemia and reperfusion model was made by suture occlusion of right middle cerebral artery. The rats were randomly assigned to nine groups: sham operated group, 6 hours and 24 hours ischemia groups, 6 hours and 24 hours reperfusion groups, corresponding NAC treatment groups. NAC groups’ rats were treated with NAC (150 mg/kg) prior to occlusion. NF-?B p65 were detected by immunohistochemistry. Brain was stained with 1% triphenyltetrazolium chloride for assessment of the volume of infarction. Apoptosis was detected by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL).Results The translocation of NF-?B from cytoplasm to nucleus increased significantly after ischemia and reperfusion. The expression of NF-?B p65 decreased in NAC pretreatment groups, which were respectively (0.462% ? 0.022%) in 6 hours ischemia-reperfusion groups, (0.452% ? 0.015%) in 24 hours ischemia-reperfusion groups, as compared with saline control groups which were (0.563% ? 0.028%) and (0.554% ? 0.013%) (P

Objective To investigate the therapeutic potential of brain-derived neurotrophic factor (BDNF) and Schwann cells(SCs) in experimental autoimmune neuritis (EAN) and assess the effect and mechanism.Methods EAN model was established by immunization of Lewis rats with 400 μg of specific peptide P2(57-81)and complete Freund adjuvant.In the therapy group,the SCs (n =28) and the combination of BDNF administration and SCs (n =48) were labeled by the nuclear fluorescent dye injected into the intracerebroventricularly in 14 d after immunization.Transplanted cell migration tracking respectively were at 25,35 and 45 days after immunization.The rats were observed for signs of disease daily and subjected to clinical score,of which the sciatic nerves were subjected to histopathological examination (hematoxylin eosinstaining,luxol-fast-green and immunohistochemical staining).The inflammatory cell infiltration and demyelination were assessed,and the CD4,CD8,CD68,S-100 and nerve growth factor (NGF) positive cells numbers were compared among the 3 different groups.Results AIl the rats had the neurological deficits.Compared with control group,there were no significant differences in SCs therapy group.In SCs + BDNF therapy group,the recovery of paralytic symptom was faster and the score was lower after immunization 45 d.After immunization 25 and 35 days,both the inflammatory cells infiltration (EAN model group:325.8 ±10.8,221.4 ± 35.2;SCs + BDNF transplantation group:307.3 ±4.6,197.2 ± 16.8; t =2.172,P =0.031 ;t=3.756,P=0.000) and the expression of CD4+,CD8+ T cells and CD68+ macrophages were reduced.After immunization 35,45 days,the demyelination degree (EAN model group:3.4 ± 0.5,2.9 ± 0.8 ; SCs +BDNF transplantation group:2.9 ±0.8,2.3 ±0.5) was reduced (t =-7.408,P =0.000;t =-6.092,P =0.000),the expression of S-100 is higher,and NGF was lower than the control group in each time point after immunization.Conclusions SCs transplanted into the cerebellar ventricle of animals can migrate into the sciatic nerve.The combination of BDNF administration and SCs transplantation may represent an effective strategy by reducing inflammation reaction,improving the expression of S-100 in the donor cell,and reducing NGF irritability heighten in sciatic nerve.However,delivery of SCs alone is inefficiency to the treatment of EAN.

AIM: To study the effect of nasal mucosal tolerance to E-selectin on cerebral ischemia-reperfusion injury.METHODS: Two different doses(single and booster) of E-selectin or PBS were dropped into membrana mucosa nasi of rats.The middle cerebral artery occlusion(MCAO) model referring to Zea Longa method with modifications was performed 48 h after the last dose of E-selectin or PBS.After 2 h ischemia and 22 h reperfusion,the numbers of CD3+CD4+T-lymphocyte and CD3+CD8+T lymphocyte subgroup in the blood were examined with flow cytometry.Rats were killed,then part of the animals was used to measure the cerebral infarction volume by TTC staining.mRNA expressions of E-selectin,ICAM-1 and lymphocyte function-associated antigen-1(LFA-1) were determined by RT-PCR and activity of SOD was determined by xanthinoxidanse method in ischemic cortex of the other part of animals.RESULTS: The ratio of the numbers of CD3+CD4+T-lymphocytes and CD3+CD8+T-lymphocytes increased in E-selectin single pretreatment group(P

0.05) ;TNF-? 0.5 ?g and TNF-? 1.0 ?g pretreatment groups showed reduced volume of lesion(all P

Interleukin-17 (IL-17) is a newly discovered proinflammatory cytokine in recent years. It has wide biological activities; therefore it may be one of the important factors in the occurrence and development of certain diseases. The article mainly reviews the current situation of the study on the related roles of IL-17 in nervous system diseases.

BACKGROUND: Nuclear factor-kappa B (NF-κB) is an important transcription factor, which can promote the transcription of many target genes after activated.OBJECTIVE: To investigate the expressions of NF-κB in local cerebral ischemia-reperfusion and the influence of the pretreatment of the N-acetylcysteine.DESIGN: Randomized grouping experiment with animals as subjects.SETTING: Department of Neurology, the Second Clinical Medical College, Harbin Medical University.MATERIALS: The experiment was finished in the Animal Experimental Center and Laboratory of Pathology of Harbin Medical University. Ninetynine male healthy Wister rats were randomly divided into 3 groups: Sham-operated group(n=l 1), saline control group(n=44), N-acetylcysteine group(n=44).METHODS: Rat models of cerebral ischemia were made with the method of thread blocking improved by Longa et al in rats of the three groups. A nylon line with a smooth spherical captular end of 0.26 mm in diameter made by heating was inserted through the cut of crotch of the common carotid artery. The prepared line for common carotid artery was tied tightly and the arteriole clamp of internal carotid artery was unclamped. The nylon line entered the common carotid artery and the inserted length of the saline control group and the N-acetylcysteine group from the crotch of the internal and external carotid artery was calculated about (18.5±0.5)mm in order to obstruct the blood supply of the middle cerebral artery. The inserted depth in sham-operated group was less than 15 mm and the blood supply of the middle cerebral artery was kept normal. Intraperitoneal injection of N-acetylcysteine was given with 150 mg/kg at 30 minutes before ischemia in N-acetylcysteine group and injection of normal saline was given with equal volume at 30 minutes before ischemia in saline control group.Eleven rats each time in saline control group and N-acetylcysteine group were killed by cutting off heads at the time points of ischemia 6, 24 hours,and reperfusion 1 hour after ischemia 6, 24 hours. The express of NF-κB of brain tissue was observed with immunchistochemical method. Percentage of cerebral infarction of rats in each group was determined by dyeing of tetrachloro red tetrazoline. Apoptosis of brain tissue cells was detected with terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL).MAIN OUTCOME MESURES: Percentage of cerebral infart volume of rats in each group, the activity of combination of the NF-κB and apoptosis of cells.RESULTS: Ninety-nine animals attended the experiment, all of them entered the final analysis. ① Percentages of infarct volume at 1 hour of ischemia and 6, 24 hours of reperfusion in N-acetylcysteine group were (8.39±2.54)%, (24.54±6.02)% respectively, and that of corresponding saline control group were (15.50±4.18)%,(32.22±3.99)%. The focus of infartion with ischemia for 24 hours in each group was increased as compared with that for 6 hours and the infarct volume in group with N-acetylcysteine was obviously decreased as compared with that in saline control group (P ＜ 0.01). ② NF-κB p56 transfered from the kytoplasm to the nucelus after the ischemia and reperfusion. The rates of p56 masculine cells in N-acetylcysteine group of ischemia for 6 and 24 hours were (0.462±0.022)%, (0.452±0.015)% respectively, the express of which was decreased as compared with that in saline control group [(0.563±0.028 )%,(0.554±0.013)%] (P ＜ 0.01 ). ③ Cells of apoptosis pretreated with N-acetylcysteine were obviously decreased as compared with that pretreated with normal saline.CONCLUSION: Focal cerebral ischemia and reperfusion can activate NF-κB p65, which participate in the damage of cerebral ischemia and reperfusion. NF-κB can inhibit the express of p65, and relieve the nerve injury and so have the effct of protection for brain.

BACKGROUND: Some studies suggest that pre-injection of tumor necrosis factor-α (TNF-α)can protect focal cerebral ischemia in mice. Cerebral ischemia tolerance is related to the increase of TNF-α level; on the other hand, TNF-α is an injurious cytokine associated with stroke. Circulating antibody against anti-TNF-α can protect reperfused injury.OBJECTIVE: To study the effects of TNF-α pretreatment and post-treatment on cerebral ischemia-reperfusion injury and explore possible mechanism.DESIGN: Randomized controlled study.SETTING: Neurological Department, the Second Hospital Affiliated to Harbin Medical University.MATERIALS: The experiment was conducted at the Animal Experiment Center of Harbin Medical University from January to April 2002. Totally 120 healthy adult male Wistar rats were randomly divided into the following 8 groups: TNF-α 0.05 μg, 0.5 μg and 1.0 μg pretreatment groups and PBS group, TNF-α 0.05 μg, 0.5 μg and 1.0 μg post-treatment groups and PBS group with 15 in each group.METHODS: The focal brain ischemia model of middle cerebral artery occlusion (MCAO) was made using inserting thread method. TNF-α of different doses (0.05 μg, 0.5 μg or 1.0 μg) or PBS was injected intracisternally and 22-hour reperfusion, 8 rats from each group were killed. Then the perhour reperfusion, 7 rats from each group were killed. Then pathological changes were observed, glial fibrillary acidic protein (GFAP) and intercellular adhesion molecule-1 (ICAM-1) expression were inspected by immunohistochemical method. Histopathological and immunohistochemical evaluation was made with the computer-assisted image analyzing system,and the number of GFAP positive cells and ICAM-1 positive vessels in each hemisphere was counted.riliary acidic protein and ICAM-1.infarct volume: TNF-α 0.5 μg and TNF-α 1.0 μg pretreatment groups showed reduced volume of lesion; infarct volume reduced by 70.9% in TNF-α 0.5 μg pretreatment rats and 66.5% in TNF-α 1.0 μg pretreatment rats. TNF-α 0.5 μg and TNF-α 1.0 μg post-treatment groups showed increased volume of lesion; infarct volume increased by 22.3% in TNF-α 0.5 μg post-treatment rats and 46.7% in TNF-α 1.0 μg post-treatment rats.TNF-α 0.05 μg and 1.0 μg pretreatment groups did not differ significantly (P ＞ 0.05), but there was an obvious difference between TNF-α 0.5 μg and pared with PBS pretreatment group, TNF-α 0.5 μg and 1.0 μg pretreatment groups showed lessened tissue damage and edema. Compared with PBS post-treatment group, TNF-α 0.5 μg and TNF-α 1.0 μg post-treatment fibriliary acidic protein and ICAM-1: TNF-α 0.5 μg and TNF-α 1.0 μg pretreatment groups showed reduced volume of glial fibriliary acidic protein and ICAM-1 (P ＜ 0.05); but TNF-α 0.5 μg and TNF-α 1.0 μg posttreatment groups showed increased volume of glial fibriliary acidic protein and ICAM-1 (P ＜ 0.05). TNF-α 0.05 μg and 1.0 μg pretreatment groups did not differ significantly (P ＞ 0.05); but there was an obvious difference between TNF-α 0.5 μg and 1.0 μg post-treatment groups (P ＜ 0.05).cerebral ischemia reperfusion injury. This effect is not related to the repair given after cerebral ischemia reperfusion, ischemia exacerbates, which is α are determined by whether TNF-αis given before or after cerebral ischemia in a dose-dependent manner.

BACKGROUND: Recent studies have proven the existence of the regeneration of central nervous tissue. But abjective results,such as lacked of neurogenesis after injury,also have been found in many experiments. The greatest difficulty in conventional brain transplantation or brain tissue transplantation has been the survival and development of the graft. Additionally,the stability of therapeutic effects and the rehabilitation of brain functions also need confirmation.OBJECTIVE: To investigate an approach to intrathecal injection of neural stem cells(NSCs) in stroke therapy,and observe therapeutic effects and side effects as well,so as to make the evaluation of the safety and feasibility.DESIGN: A confirmative before-after study based on stroke patients.SETTING: A neurology department in a municipal hospital and a microbiology and immunology department affiliated to a university hospital.PARTICIPANTS: From November 2002 to September 2003,26 stroke inpatients in the Neurology Department of Anyang Municipal People' s Hospital were selected. Of all the c ases,3 were diagnosed as acute cerebral hemorrhage,and the other 23 had been suffering strokes for durations ranging from 3months to 30 years,an average of (4.2 ± 6. 6) years. They were 20 male and 6female between the ages from 36 -72 years old,an average of(56.3 ± 12.7)years old. Fifteen of them were ischemic and 11 were hemorrhagic. Nineteen were associated with hypertension,2 with coronary heart disease,4 with diabetes and 4 associated with hyperlipodemia.INTERVENTIONS: On each of the 3 patients with acute cerebral hemorrhage (hematoma volume,35 - 40 mL),a microinvasive intracerebral hematoma puncture was performed,and then a suspension of NSCs were conducted to the stroke by a drainage tube. For the rest of the patients,suspensions were intrathecally administered into the subarachnoid and then flowed to the cerebral surface through cerebrospinal fluid(CSF) circulation. Afterwards,physical therapy(PT),occupational therapy (OT) and speech therapy(ST) were jointly applied to facilitate the rehabilitation of the stroke patients. Therapeutic effects was calculated according to the European stroke scale(ESS) and the Barthel Index(BI) . If ESS index went beyond or equal to 1 score,the case would be defined as effective; otherwise,it would be defined as not effective. Additionally,CT,MRI,EEG,chest x-ray,and blood biochemical variables were also measured.MAIN OUTCOMEMEASURES: Therapeutic effects and side effects were taken as main outcomemeasurements.RESULTS: Of the 23 patients who ntrathecal administration,19had positive therapeutic effect and 4 did not. Post-transplantation ESS was higher than that of pre-transplantation(54. 1 ±21.2 vs 51.4 ±21.1,t = 5.8,P = 0. 000 007 6),while post-transplantation BI also increased significantly as compared with that of pre-transplantation(41.1 ± 31.3 vs 36. 1 ± 32. 1,vasive intracerebral hematoma puncture had successful rehabilitation and regained self-care ability. Of all the patients,4 got a transitory fever and 2felt slight post-operation headache.CONCLUSION: Conclusion can be drawn from the study that stroke patients are ameliorated to various extents after neural stem cell transplantation which has no toxicity or side effects. It shows that neural stem cell transplantation is viable and feasible in improving the motor function and self-care ability in stroke patients.