Intracerebroventricular injection of Aβ 1-42 combined with two-vessel occlusion accelerate Alzheimer's disease development in rats.

Numerous experimental studies and clinical observations suggest that cerebral ischemia may contribute to the pathogenesis of Alzheimer's disease (AD). Two-vessel occlusion caused cerebral ischemia model is often used in the study of vascular dementia (VaD). But how cerebral ischemia works on AD rat model which induced by intracerebroventricular injection of Aβ1-42 remains unclear. In the following study, we investigated the characteristics of rat model caused by intracerebroventricular injection of Aβ1-42 or two-vessel occlusion (2-VO) only and by both of the two operations. The animal cognitive functions were accessed by the Morris water maze. Regional cerebral blood flow was detected by Laser Doppler Blood Flowmeter. HE&Nissl staining, Congo red staining and immunohistochemistry were used to observe the status of neuronal loss, Aβ deposition and the phosphorylated tau expression in hippocampus, respectively. We also measured the contents of AchE and ChAT in serum and hippocampus by Enzyme Linked Immunosorbent Assay. The MWM results showed that rats of Aβ1-42 +2-VO group had a disorder in cognitive functions, at an early stage of one week after modeling, comparing with rats of sham group. The regional cerebral blood flow (rCBF) was significantly reduced in Aβ1-42 +2-VO and 2-VO group one week after modeling, and still maintained low perfusion levels four weeks after modeling. HE and Nissl staining showed that Aβ1-42 +2-VO rats' hippocampal CA1 neurons were in disorder, degeneration and necrosis, severe neuronal loss from the first week to the fourth week, while this phenomenon only appeared in the fourth week after modeling in rats of Aβ1-42 group and 2-VO group. Congo red staining showed that Aβ1-42 + 2-VO group rats' hippocampus CA1 had amyloid deposits from the first week to the fourth week, Aβ1-42 group were not find amyloid deposition significantly until four weeks after modeling, however, 2-VO group had no significant amyloid deposition all the time. Notably, IHC showed that, two weeks after modeling, the p-tau positive total area and integrated optical density of hippocampal CA1 region were significantly increased in Aβ1-42 + 2-VO group rats, while 2-VO group and Aβ1-42 group rats had no significantly changes all the time. We also found that the content of AchE was increased both in serum and hippocampus of Aβ1-42 + 2-VO group rats, and ChAT was decreased. However, there was no significantly change in cortex of content of AchE: acetylcholinesterase (AchE) and choline acetylase (ChAT) all three groups. Together, our study suggest that intracerebroventricular injection of Aβ1-42 combined with two-vessel occlusion may accelerate Alzheimer's disease development in rats. Also, this may serve as a less-time consuming new model to study the Alzheimer's disease and especially AD accompanied by cerebral ischemia.