β-amyloid accumulation in neurovascular units following brain embolism

Feng Han, Kohji Fukunaga

研究成果: Review article査読

6 被引用数 (Scopus)

抄録

Nitric oxide (NO) toxicity is in part mediated by generation of peroxynitrite with concomitant production of superoxide under pathological brain conditions such as ischemia and Alzheimer's disease. The pathophysiological relevance of endothelial nitric oxide synthase (eNOS) to brain embolism-induced neurovascular injury has not been documented. We found that microsphere embolism (ME)-induced aberrant eNOS expression in vascular endothelial cells likely mediates blood-brain barrier (BBB) disruption via peroxynitrite formation and in turn causes brain edema. We also demonstrated that a mild ME model was useful for investigating the sequential events of neurovascular injury followed by β-amyloid accumulation and tau hyperphosphorylation. Indeed, immunoblotting of purified brain microvessels revealed that β-amyloid accumulation significantly increased one week after ME induction and remained elevated for twelve weeks in those animals. Moreover, we also confirmed that peroxynitrite formation and eNOS uncoupling-mediated superoxide generation in microvessels are inhibited by a novel calmodulin inhibitor. Thus, peroxynitrite formation via elevated eNOS is associated with endothelial cell injury with concomitant β-amyloid accumulation in microvessels of aged rats. In this review, we focus on the detrimental effects of eNOS expression following brain embolism and introduce an attractive model representing progressive Alzheimer's disease pathology in brain.

本文言語English
ページ(範囲)101-109
ページ数9
ジャーナルJournal of Pharmacological Sciences
111
2
DOI
出版ステータスPublished - 2009

ASJC Scopus subject areas

  • 分子医療
  • 薬理学

フィンガープリント

「β-amyloid accumulation in neurovascular units following brain embolism」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル