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

Author(s): Munehisa Shimamura, Naoyuki Sato, Hironori Nakagami, Mariana Kiomy Osako, Mariko Kyutoku, Kouji Wakayama, Ryuichi Morishita.

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization)
(Formerly Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents)

Volume 13 , Issue 1 , 2013

Abstract:

Although the linkage between vascular dysfunction and Alzheimer’s disease has received much attention, the influence of beta-amyloid (Aβ) deposits on microcirculation in the chronic stage of ischemic brain injury is unknown. To examine the relationship of Aβ with the microcirculation around Aβ deposits in the chronic stage of cerebral infarction, Wistar rats were exposed to permanent middle cerebral artery occlusion (MCAo). Microangiography using albuminfluorescein isothiocyanate was performed 3 months after MCAo, followed by immunohistochemistry with GFAP and Aβ. 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 Aβ 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 Aβ deposits. Conversely, enlarged low-density microvessels with less reactive gliosis were observed in the Aβ deposits. Because the regions with reactive gliosis without Aβ deposits showed no changes in microcirculation and previous reports showed the proangiogenic and anti-angiogenic effects of Aβ in in vitro studies, we hypothesize that continuous Aβ deposits act directly on microvessels, rather than via reactive gliosis. Although further studies are necessary, therapeutic approaches to reduce Aβ deposits might be a promising approach to improve microcirculation in the thalamus in the chronic stage of ischemic stroke.

Keywords: Amyloid Aβ, angiogenesis, blood-brain-barrier, cerebral ischemia, gliosis, microcirculation, microvessels, middle cerebral artery occlusion, thalamus, APP23.

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Article Details

VOLUME: 13
ISSUE: 1
Year: 2013
Page: [77 - 80]
Pages: 4
DOI: 10.2174/1871522211313010008

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