Effect Of Aβ25-35 Intraventricular Injection On Acute Stroke In Mice

Alzheimer’s disease is a progressive neurodegenerative disease.Its major pathological hallmarks are amyloid plaque formed of Aβ in parenchyma and the neurofibrillary tangles formed by tau protein phosphorylation,accompanied by loss of neurons and synapses.Numerous clinical and epidemiological reports indicate that stroke is a cerebrovascular disease and risk factor for Alzheimer’s patients.Alzheimer’s patients are prone to suffering stroke,and more severe damage after stroke.However,in the latest research there are rare information available addressing pathological mechanism of Alzheimer’s susceptibility to stroke.In the current study,we investigated the effect of Aβ25-35 on stroke damage and combined the mouse model of ischemic stroke with intraventricular injection of toxic Aβ.In this experiments we used four groups of mice,vehicle group,Aβ25-35 group,vehicle/stroke group and Aβ25-35/stroke group.We evaluated the motor function of mice by rotarod test,open field test and grip strength test.Brain slice of 30 μm were obtained from Leica vibrate tome VT 1000 and used for Nissl staining to measure the infarct volume at 3 days after stroke.Immunocytochemistry staining was used to examine the reaction of the degenerative neurons and astrocytes.Moreover,western blotting was used to measure relative content of GFAP and Claudin-5.Results showed that infarct volume of Aβ25-35/ischemia was significantly larger than the vehicle/stroke.The vehicle,Aβ25-35,vehicle/stroke and Aβ25-35/ischemia group showed no significant differences in open field test but grip strength test results showed that vehicle/ischemia and Aβ25-35/ischemia groups had significant reduction compared to vehicle group and Aβ25-35 group,respectively.However,there were no significant differences between vehicle/stroke group and Aβ25-35/ischemia group.Compared with vehicle/ischemia group,Aβ25-35/ischemia group showed significant reduction in rotarod time.The density of degenerative neurons in Aβ25-35/ischemia group was significantly higher than vehicle/ischemia group.The density of microglia in Aβ25-35/ischemia group was significantly increased.In the Aβ25-35/ischemia group,we found a reduction in the expression of Claudin-5 and an increase in GFAP expression.Our results indicated that intraventricular injection of Aβ25-35 in mice exacerbated cerebral infarction and aggravated motor dysfunction after stroke.Severe injury might be related to the toxicity of Aβ25-35,or caused by inflammatory response induced by microglia and astrocytes after combined treatment of Aβ25-35 and ischemia.These findings provide a theoretical basis for understanding the pathogenesis of Alzheimer’s disease and pathological mechanism of stroke.