There are few studies on the neuroprotective effects of syringaldehyde in a rat model of cerebral ischemia. The study aimed to elucidate the mechanisms underlying the neuroprotective effects of syringaldehyde on ischemic brain cells. Rat models of cerebral ischemia were intraperitoneally administered syringaldehyde. At 6 and 24 hours after syringaldehyde administration, cell damage in the brain of cerebral ischemia rats was obviously reduced, superoxide dismutase activity and nuclear respiratory factor 1 expression in the brain tissue were markedly increased, malondi-adehyde level was obviously decreased, apoptosis-related cysteine peptidase caspase-3 and -9 immunoreactivity was obviously decreased, and neurological function was markedly improved. These ifndings suggest that syringaldehyde exerts neuroprotective effects on cerebral ischemia injury through anti-oxidation and anti-apoptosis.

A preliminary study from our research group showed that picroside II inhibited neuronal apop-tosis in ischemic penumbra, reduced ischemic volume, and improved neurobehavioral function in rats with cerebral ischemia. The aim of the present study was to validate the neuroprotective effects of picroside II and optimize its therapeutic time window and dose in a rat model of ce-rebral ischemia. We found that picroside II inhibited cell apoptosis and reduced the expression of neuron-speciifc enolase, a marker of neuronal damage, in rats after cerebral ischemic injury. The optimal treatment time after ischemic injury and dose were determined, respectively, as fol-lows:(1) 2.0 hours and 10 mg/kg according to the results of toluidine blue staining;(2) 1.5 hours and 10 mg/kg according to early apoptotic ratio by lfow cytometry;(3) 2.0 hours and 10 mg/kg according to immunohistochemical and western blot analysis;and (4) 1.5 hours and 10 mg/kg according to reverse transcription polymerase chain reaction. The present ifndings suggest that an intraperitoneal injection of 10 mg/kg picroside II 1.5-2.0 hours after cerebral ischemic injury in rats is the optimal dose and time for therapeutic beneift.

Transient brain ischemia has been shown to induce hyperphosphorylation of the microtu-bule-associated protein tau. To further determine the mechanisms underlying these processes, we investigated the interaction between tau, glycogen synthase kinase (GSK)-3β and protein phos-phatase 2A. The results confirmed that tau protein was dephosphorylated during brain ischemia;in addition, the activity of GSK-3βwas increased and the activity of protein phosphatase 2A was de-creased. After reperfusion, tau protein was hyperphosphorylated, the activity of GSK-3β was de-creased and the activity of protein phosphatase 2A remained low. Importantly, the interaction of tau with GSK-3β and protein phosphatase 2A was altered during ischemia and reperfusion. Lithium chloride could affect tau phosphorylation by regulating the interaction of tau with GSK-3βand pro-tein phosphatase 2A, and improve learning and memory ability of rats after transient brain ischemia. The present study demonstrated that it was the interaction of tau with GSK-3β and protein phos-phatase 2A, rather than their individual activities, that dominates the phosphorylation of tau in tran-sient brain ischemia. Hyperphosphorylated tau protein may play an important role in the evolution of brain injury in ischemic stroke. The neuroprotective effects of lithium chloride partly depend on the inhibition of tau phosphorylation during transient brain ischemia.

脑缺血后GDNF的表达与应用的研究进展

胶质细胞源性神经营养因子(GDNF)具有广谱性神经营养作用.在脑缺血后组织修复的研究中,发现GDNF参与神经修复过程.在几种脑缺血模型中均可见到该蛋白基因的mRNA或蛋白本身及其受体表达.在给以外源性的GDNF实验中,发现此蛋白在脑缺血时表现出强大的神经保护作用,使脑梗塞面积减小,脑水肿程度减轻,存活神经元数明显增加,显示出良好的应用前景.

热休克蛋白表达对缺血性脑损伤的保护作用

Heat shock protein is a group of stress protein produced under ill state. It can protect normal cells from damages caused by bad stimulates. It is thought as one of substance basis that remain in the process of evolution and take effect of anti damage. Now it is paid attentions as neuron protective substance induced by cerebral ischemic preconditioning.

BACKGROUND: Cerebrovascular disease often causes dysfunction of the brain nerve, and nerve cel apoptosis is the important factor of cerebral nerve dysfunction. The excessive expression of c-fos can block the transduction of intracelular signal so that producing some apoptosis-promoting factors, which involve in nerve cel apoptosis process after ischemia injury of brain. Bcl-2 is an inhibited factor. It might to be the key to treat ischemic cerebrovascular disease by inhibiting or reducing the apoptosis of nerve cels after ischemia injury. OBJECTIVE: To investigate the therapeutic effect and mechanism of the Total Flavone of Hawthorn Leaf on chronic cerebral ischemia rats. METHODS: A total of 72 healthy male Sprague-Dawley rats were randomly divided into sham surgery group, model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Permanent bilateral carotid artery ligation was used to prepare chronic cerebral ischemia model in the model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Total Flavone of Hawthorn Leaf group and ginkgo leaf group respectively received 140 mg/kg Total Flavone of Hawthorn Leaf and 12.3 mg/kg ginkgo leaf intragastricaly for 36 days from 36 days after model induction. Model group and sham surgery group received 3.5 mL/kg physiological saline intragastricaly. RESULTS AND CONCLUSION: Compared with the model group, the expression of c-fos protein significantly deceased in the Total Flavone of Hawthorn Leaf group (P < 0.01), Bcl-2 expression levels significantly increased (P < 0.01), and Ca2+ content decreased (P < 0.05). Moreover, no significant difference in above indexes was detected between Total Flavone of Hawthorn Leaf group and ginkgo leaf group (P> 0.05). These data indicated that the protective effect of Total Flavone of Hawthorn Leaf on chronic cerebral ischemia was associated with its inhibition of neuronal apoptosis. Its mechanism of anti-apoptosis might be associated with up-regulating expression of Bcl-2, down-regulating expression of c-fos and decreasing Ca2+ content in brain.

Autophagy is a lysosome-mediated degradation process for non-essential or damaged celular constituents, playing an important homeostatic role in cel survival, differentiation and development to maintain homeostasis. Autophagy is involved in tumors as wel as neurodegenerative, cardiovascular and cerebrovascular diseases. Recently, active compounds from traditional Chinese medicine (TCM) have been found to modulate the levels of autophagy in tumor cels, nerve cels, myocardial cels and endothelial cels. Ischemic stroke is a major cause of neurological disability and places a heavy burden on family and society. Regaining function can signiifcantly reduce dependence and improve the quality of life of stroke survivors. In healthy cels, autophagy plays a key role in adapting to nutritional deprivation and eliminating aggregated proteins, however inappropriate activation of autophagy may lead to cel death in cerebral ischemia. This paper reviews the process and the molecular basis of autophagy, as wel as its roles in cerebral ischemia and the roles of TCM in modulating its activity.

AIM: To study the protecitve mechanism of Ligustrazine (LT), Shenmai Parenteral Injection (SPI), combination of Ligustrazine and Shenmai Parenteral Injection (LSP) to myocardial injury after brain ischemia-reperfusion in aged rats from the change in ATPase and free radical in order to provide theoretical basic for prevention and cure of cerebral infarction. METHODS: Aged rats (more than 20 months) were divided into model group, control group, Nimotop group, LT group, SPI group and LSP group. We measured the following items in aged rats with 60 min of reperfusion after 30 min of brain ischemia: the content of MDA, the activities of superoxide dismutase (SOD), lactic dehydrrogenase (LDH), creatine phosphokinase (CPK), ATPase. RESUTLS: The CPK and LDH activities in the model rats increased obviously. The serum CPK activity in the LSP group, the LT group, nimotop group was lower than those in the model group obviously. The serum LDH activities in LT group and SPI group were obviously lower compared with those in the model group. The activity of Na＋-K＋-ATPase and Ca2＋-ATPase in model group was decreased. Contrast to the model group, the activity of Na＋-K＋-ATPase in LSP group, Nimotop group, LT group and the activities of Ca2＋-ATPase in the LSP group were higher. The serum MDA/SOD ratio was larger than that in the control group. The decrease in myocardial SOD activity and the increase in the MDA level, MDA/SOD ratio in the model group showed significant difference compared with that in the control. The MDA level in the LSP group was lower than that in the model group. The increase in myocardial SOD activity and decrease in MDA, MDA/SOD ratio were obvious in the LSP group compared with the model group. CONCLUSION: The myocardial injury after brain ischemia-reperfusion in aged rats was related to the decrease in the activity of Na＋-K+-ATPase and injury of free radical. LT, SPI, LSP and Nimotop could prevent this inury. Nimotop and LT could enhanced the activity of Na+-K+-ATPase obviously. SPI could enhance the activity of Ca2＋-ATPase and restrain the injury of free redical and lipid peroxidation. This may be the mechanism of restraining myocardial injury after brain ischemia-reperfusion.

AIM: To study the mechanism of myocardial injury after brain ischemia-reperfusion in aged rats from the changes in Dopamine (DA), Noradrenalin (NE), Epinephrine(E) and Neuropeptide Y(NPY).METHODS: Young (5 months) and aged (20 months or more) rats were divided into model groups and normal control groups, respectively. We observed the following items in rats with 60 minute reperfusion after 30 minute brain ischemia: the pathological changed of myocardium, the activities of lactic dehydrrogenase(LDH), creatine phosphokinase(CPK), the contents of NE, DA, E, NPY. RESULTS:The CPK and LDH activities in the young model rats were higher than those in the young control rats was higher than that in the young control rats (P＜0.05). The serum CPK activity in the aged control rats was higher than that in the young control rats (P＜0.05). The myocardial CPK activity was higher in the aged model rats compared with the young molel rats (P＜0.05) and was higher in aged control rats compared with the young control rats (P＜0.01). The myocardial LDH activity was lower in the aged control rats than that in the young control rats (P＜0.05) and aged model rats (P＜0.01). The serum NE level, the level of NE and DA in the hypothalamus were higher obviously than those in the young control rats. The serum NE contents in the two model groups (young and aged) were higher respectively than the two control rats (young and aged). The following items’ contents were higher in the aged model rats than in the young model rats: serum NE, serum E, hypothalamus NE. The hypothalamus NE and E content was lower in the aged model rats than in te aged control rats. NPY level in the brain tissue was lower in the aged control rats than that in the young control rats and aged model rats (P＜0.05).CONCLUSION: The myocardial injury after brain ischemia-reperfusion was concerned with the enhanced excitability of sympathetic-adrenal system, espectially in the aged rats. However, the change in myocardial enzyme was not serious in the aged rats compared with young rats.

氯胺酮,咪唑安定,硫喷妥钠和异丙酚对大鼠皮层脑片缺血性损伤的作用

AIM: To compare the effects of ketamine, midazolam, thiopental, and propofol on brain ischemia by the model of oxygen-glucose deprivation (OGD) in rat cerebral cortical slices. METHODS: Cerebral cortical slices were incubated in 2 % 2,3,5-triphenyltetrazolium chloride (TTC) solution after OGD, the damages and effects of ketamine,midazolam, thiopental, and propofol were quantitativlye evaluated by ELISA reader of absorbance (A) at 490 nm,which indicated the red formazan extracted from slices, lactic dehydrogenase (LDH) releases in the incubated supernate were also measured. RESULTS: Progressive prolongation of OGD resulted in decreases of TTC staining.The percentage of tissue injury had a positive correlation with LDH releases, r=0.9609, P＜0.01. Two hours of reincubation aggravated the decrease of TTC staining compared with those slices stained immediately after OGD (P＜0.01). These four anesthetics had no effects on the TTC staining of slices. Ketamine completely inhibited the decrease of A value induced by 10 min of OGD injury. High concentrations of midazolam (10 μmol/L) and thiopental (400 μmol/L)partly attenuated this decrease. Propofol at high concentration (100 μmol/L) enhanced the decrease of A value induced by 10 min of OGD injury (P＜0.01). CONCLUSION: Ketamine, high concentration of midazolam and thiopental have neuroprotective effects against OGD injury in rat cerebral cortical slices, while high concentration of propofol augments OGD injury in rat cerebral cortical slices.

短暂脑缺血诱导成年大鼠纹状体内CRMP-4的表达

AIM: To study the expression of collapsing response mediated protein-4 (CRMP-4) and nestin in the ischemic adult rat brain following transient brain ischemia. METHODS: Brain ischemia was induced by transient left middle cerebral artery occlusion (MCAO) for 60 min in adult rats. The expression of CRMP-4, nestin and bromodeoxyuridine (BrdU) was analyzed by immunohistochemical method. The co-localization of CRMP-4 and nestin or BrdU was analyzed by double staining combined with confocal laser scanning microscopy. RESULTS: CRMP-4, a marker of immature neuron, could be expressed in the ipsilateral striatum and cerebral cortex at 1st and 2nd week after the ischemia-reperfusion; nestin, a marker of neural stem cell, occurred in above regions from several hours to 2 weeks. CRMP-4 costained with nestin and with BrdU incorporation. CONCLUSION: Neural stem cells may present in the striatum and cerebral cortex of adult rat and can be triggered to differentiate into newborn neuron there by ischemic brain trauma.

白三烯受体拮抗剂ONO-1078对大鼠短暂性全脑缺血的神经保护作用

AIM: To determine whether ONO-1078 {pranlukast, 4-oxo-8-[p-(4-phenylbutyloxy)benzoyl-amono]-2-(tetrazol 5-yl)-4H-1-benzopyran hemihydrate}, a potent leukotriene receptor antagonist, possesses a neuroprotective effect on global cerebral ischemia in rats, and to explore its possible mechanism of action. METHODS: Transient global cerebral ischemia was induced by four-vessel occlusion for 10 min and followed by 72-h reperfusion. ONO-1078 (0.03-0.3 mg/kg) and edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one, a neuroprotective agent) 10 mg/kg were ip injected 30 min before ischemia and 1 h after reperfusion, and once a day afterward. Neurological outcome was evaluated before ischemia and 24, 48, 72 h after reperfusion. Neuron density, the expressions of N-methyl-D aspartate (NMDA) receptor subunit proteins (NR1, NR2A, NA2B) and vascular cell adhesion molecule 1 (VCAM-1) in the cerebral cortex and hippocampus were measured at 72 h after reperfusion. RESULTS: ONO-1078 (0.1, 0. 3 mg/kg) and edaravone (10 mg/kg) improved ischemia-induced neurological deficiency and reduced neuron death. ONO-1078 (0.1, 0.3 mg/kg) significantly inhibited the enhanced expression of NMDA receptor subunit protein NR2A in the cortex and VCAM-1 in the hippocampus of ischemic rats. CONCLUSION: ONO-1078 possesses a neuroprotective effect on global cerebral ischemia in rats, and its mechanism may be partly related to the inhibition of the upregulation of NR2A and VCAM- 1 in different regions of the brain.

Objective:　To evaluate the effect and safety of early moderate hypothermia therapy (MHT) on patients with head injury by using parallel-control test.　　Methods:　Thirty patients with severe head injury within 6 hours after accidents were treated by MHT generally for 4-10 days. The other 30 patients with similar head injury treated routinely were enrolled for a parallel-control test. The mortality, morbidity and changes of some neuro-functional indexes as Glasgow Coma Scores, and Glasgow Outcome Scale, levels of endothelin and some other factors of neurobiochemistry in blood plasma were observed. Meanwhile, the dynamic monitoring by transcranial Doppler ultrasonography was conducted in these patients.　　Results:　The mortality in MHT group was significantly lower than that in control group. MHT not only reduced endothelin but also increased the brain biochemical factors, which were helpful to the protection of neurons in the early brain ischemia after head injury.　　Conclusions:　Early MHT can help reduce mortality and morbidity in patients with acute head injury.