Chronic Deposition of Ap Influences Microcirculation in the Chronic Stage of Cerebral Ischemia

摘要

Although the linkage between vascular dysfunction and Alzheimer's disease has received much attention, the influence of beta-amyloid (Ap) deposits on microcirculation in the chronic stage of ischemic brain injury is unknown. To examine the relationship of Ap with the microcirculation around Ap deposits in the chronic stage of cerebral infarction, Wistar rats were exposed to permanent middle cerebral artery occlusion (MCAo). Microangiography using albumin-fluorescein isothiocyanate was performed 3 months after MCAo, followed by immunohistochemistry with GFAP and Ap. Two types of atrophic changes were observed in the thalamus of ischemic brains: mild atrophy and severe atrophy with tissue defects. In both types, the deposition of Ap was observed in the ventroposterior lateral and ventroposterior medial nuclei of the thalamus. Although various patterns of microcirculation were observed in the thalamus, a high density of enlarged microvessels with reactive gliosis was often observed around Ap deposits. Conversely, enlarged low-density mi-crovessels with less reactive gliosis were observed in the AJ3 deposits. Because the regions with reactive gliosis without Ap deposits showed no changes in microcirculation and previous reports showed the proangiogenic and anti-angiogenic effects of Ap in in vitro studies, we hypothesize that continuous Ap deposits act directly on microvessels, rather than via reactive gliosis. Although further studies are necessary, therapeutic approaches to reduce Ap deposits might be a promising approach to improve microcirculation in the thalamus in the chronic stage of ischemic stroke.