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BACKGROUND: Repetitive brief and non-lethal cerebral ischemia can produce cumulative neuronal damage and vascular dementia; however, precisely injured patterns and mechanisms are still unclear. Thalamus is an important structure of learning and memory; meanwhile, it is also one of the selectively vulnerable regions of cerebral ischemia.However, there are a few reports about neuronal damage induced by repetitive cerebral ischemia.OBJECTIVE: To investigate the pathological damage and mechanism of neurons induced by repetitive cerebral ischemia in thalamus.DESIGN: Randomized controlled experimental study.SETTING: Department of Neurology, General Hospital of Chengdu Military Area Command of Chinese PLA.MATERIALS: The experiment was carried out at the Animal Central Laboratory of the Third Military Medical University of Chinese PLA from March to December 1999. A total of 72 healthy male Wistar rats were randomly divided into sham operation group, single cerebral ischemic group,repetitive cerebral ischemic group, MK-801 treatment group and saline group.METHODS: Transient global cerebral ischemia models of rats were established with modified Pulsinelli-4 vessel occluing method for single 15-minute ischemia and repetitive three 5-minute ischemia at hourly intervals,followed by 5 hours, 2 days and 4 days of survival. Rats in sham operation group were not treated with burning vertebral artery and clipping common carotid artery. 45Ca autoradiography and light microscopy were used to determine the calcium accumulation and neuronal pathological changes of thalamus following repetitive cerebral ischemia as compared with single cerebral ischemia. The effects of MK-801, a N-methyl-D-aspartate (NMDA)receptor antagonist, were also examined.MAIN OUTCOME MEASURES: Distribution and degree of calcium accumulation and neuronal damage in the thalamus of rats in each group.RESULTS: Sham-operated rats revealed no abnormal calcium accumulation and neuronal damage in the thalamus. At 5 hours following ischemia,slightly abnormal calcium accumulation was found in the partial thalamus of the repeated ischemic group, and the neuronal damage was also relatively severer than that in the single ischemic group (0.98±0.19, 0.60±0.14, P＞ 0.05). At 2 days after ischemia, obviously abnormal calcium accumula tion and neuronal damage were shown in thalamus, and the degree of calcium accumulation and score of neuronal damage in repeated ischemic group were significantly severer than that in single ischemic group (1.62±0.31, 0.88±0.21, P ＜ 0.01). At 4 days, the thalamus calcium accumulation and neuronal damage were further increased, and also that in repeated ischemic group was significantly severer than that in single ischemic group (1.80±0.21, 1.02±0.23, P ＜ 0.01), especially marked calcium accumulation and cumulative damage were shown in the ventral thalamus. MK-801 significantly relieved the abnormal calcium accumulation and neuronal damage in the thalamus in repeated ischemic group, showing significant protection of thalamus neurons as compared with that in saline-treated group (0.20±0.12, 1.80±0.15, P ＜ 0.01).CONCLUSION: Repetitive non-lethal cerebral ischemia results in an intense cumulative damage in the ventral thalamus, and the excitatory amino acid and Ca2+ may play a major role in it.
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Objective To explore the possible mechanism by which protein kinase C (PKC) involves in the neuronal apoptosis induced by cerebral ischemia/reperfusion Methods After the model of ischemia/reperfusion was established in male Wistar rats, PKC activity, FOS protein expression and neuronal apoptosis in their brains were observed The effect of PKC inhibitor, Dengzhanghua, on above indexes were studied at the same time Results Cerebral ischemia/reperfusion resulted in transloactional activation of PKC, accompanied with the increase of FOS expression and neuronal apoptosis Dengzhanghua prevented against the above changes Conclusion Activated PKC is involved in ischemia/reperfusion induced neuronal apoptosis by regulating FOS expression
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AIM:To study pharmacokinetic of Pueraria Flavonid Nasal Drop in rabbits through nasal administration in comparison with oral administration. METHODS:Ten New Zealand rabbits were divided into two groups randomly and administrated nasally and orally (106.4 mg/kg of pueraria flavonid). HPLC was adopted to detect pueraria flavonoid content and DAS 2.0 was used to calculate bioavailability. RESULTS:The main pharmacokinetic parameters of nasal and oral administrations were AUC (0-∞)1 =(30.55?4.93)mg/(L?h),T max1 =(0.90?0.14)h,C max1 =(11.27?1.66)mg/L;AUC (0-∞)2 =(6.90?2.76)mg/(L?h),T max2 =(0.63?0.34)h,C max2 =(1.68?0.84)mg/L. Relative bioavailability of nasal delivery was 442.8%. CONCLUSION:Pueraria Flavonoid Nasal Drop is well absorbed in rabbits and has high bioavailability.
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The clinical features and plasma malondialdehyde(MDA) contents were studied in 91 patients with acute cerebral vascular disease (ACVD). The cerebrospinal fluid (CSF) MDA contents were also measured in 51 of them. The MDA contents increased significantly more than that of the control group. The difference of CSE MDA between the disease group and control was more significantly than that of plasma. It may be due to the fact that the CSE MDA level reflects the severity of lipid peroxidative reaction (LPR) in brain directly, whereas plasma MDA level reflects the severity of systemic LPR. The dynamic change of plasma MDA is closely related to the outcome of the disease. The plasma MDA decreases in ameliorated patients, but increases in the aggravated. The measurement of palsma MDA may be used as an indicator to predict the prognosis of ACVD.
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The selective vulnerability of brain tissues after 30 minutes of complete ischemia was observed 5, 15, and 30 minutes after ischemia and 15, 60, and 180 minutes after reperfusion in rats under optical and electron microscopies. It was found that the cerebral cortex especially the third and fifth lamina, the H1 segment of the hippocampus, and the Purkinje cells of the cerebellum were most liable to be damaged after ischemia. After reperfusion, the alterations of membrane system, nuclei and organelles were significant. The membraneous structures which contained a large amount of lipids were more severely damaged. At the same time cerebral edema was found, the severity of which was correlated with the intensity of histopathological and ultrastructural changes of the brain and the degree of blood brain barrier disruption.The findings suggest that oxygen free radicals and lipid peroxides may play an important role in the development of the damages in the brain mentioned above after reperfusion.
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The dynamic changes of the contents of polyamines and excitatory amino acid in the hippocampus during cerebral ischemia and reperfusion were observed in rats.It was found that the content of putrescine was increased and the release of excitatory amino acid elevated during reperfusion,and the increase of putrescine could be stopped when the antagonist of NM-DA receptor of excitatory amino acid,that is,MK-801,was administered.These facts suggest that the metabolic disturbance of polyamines in closely related to the release of excitatory amino acid and modulated by NMDA receptors.The combination of polyamines with excitatory amino acid may play an important role in the ischemic damage of the brain.