| Cerebrovascular disease especially ischemic brain damage has a high incidence in the aged people.The traditional view that a cerebral ischemia especially transient cerebral ischemia and Alzheimer's disease (Alzheimer's disease, AD) is a separate disease. In clinical practice, mainly by cerebral ischemia caused by vascular dementia (Vascular Dementia, VaD) and AD was divided into two different types of dementia. However, in recent years a number of clinical retrospective study found that risk factors for cerebral ischemia associated with high incidence of AD is associated. Have a history of cerebral infarction in patients with AD, the occurrence probability and degree of cognitive impairment were significantly higher than the patient only suffering from AD. In addition, some animal studies have also found a focal cerebral ischemia-reperfusion injury in animal models can show some of the pathological features of AD. Speculated, AD is closely related with cerebral ischemia.Study the Effect of cerebral ischemia and may contribute to the early prevention and treatment of AD.Axonopathy in AD and other neurodegenerative diseases caused widespread concern. It includes swollen axons and axonal transport injury.Such changes have been identified in living AD patients and postmortem AD brains and in different animal models. Moreover, the axonal defects in mouse models of AD were identified to precede known disease-related pathology including neurofibrillary tangle (NFTs) and senile plaque (SP) by more than a year. Up to now, no study has been reported to investigate axonal changes after transient focal ischemia.In our study, we observed the morphological changes of axons of neurons in different areas of ischemic hemisphere following ischemia/reperfusion (I/R) in order to explore the importance of cerebral ischemia on the risk AD. We also examined the expression of cerebral ischemia on the amount and the distribution of Aβand Tau protein.Our study may provided a new research line to study the pathological mechanism of AD.MethodMale Wistar rats were subjected to middle cerebral artery occlusion for 30 min; BDA was injected into the different brain areas (cortex, hippocampus and striatum) of rat by In Vivo Tracing used by microsyringe pump. The morphology feature of the axon showed by BDA was assessment; and Aβ42,phosphorylated Tau was examined by immunohistochemistry and WesternBlot at 6h,24h, 1w,2w,3w and 4w after MCAO.Results1. At the initiation of MCAO, swollen axons and varicosities appeared in the ischemic sensory and motor cortex as compared to the corresponding contra-lateral regions and sham-operated group. The axons of projection fibers in the peri-lesional cortex, hippocampus and caudoputamen presented the similar changes. Moreover, these morphological changes of axons and varicosities in the ischemic side were always observed from 6 h up to 4 w after MCAO. Semi-quantitative analysis of axonal changes showed that axonal damages had not improved gradually at extended time and the degree of swollen axons and varicosities was particularly significant at 2 weeks after reperfusion.2. We did not observe the classic Aβplaques and overexpression of Aβ42 within and/or close to some swollen axons, varicosities or axonal terminals in the ischemic brain regions at each time point after reperfusion, nevertheless, weak Tau protein staining could be detected within the ischemic and peri-lesional cortex. No significant increase in Tau protein expression was found in the ischemic hippocampus and caudoputamen. The result of Western blotting showed that there was an enhancement of Tau phosphorylation at 6 h after reperfusion. The level of AT8 was increased significantly in the ischemic cortex of MCAO group compared to the ipsilateral side of other MCAO groups at 1 week after reperfusion.ConclusionThis study found that transient cerebral ischemia can induce axonal and varicosity swelling; in addition, phosphorylated tau expression in cortex was increased, and there are links in time and spaces. |
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