Rapid Loss of Microvascular Integrin Expression during Focal Brain Ischemia Reflects Neuron Injury

DOI Web Site Web Site 被引用文献6件
  • Masafumi Tagaya
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, U.S.A.
  • Hans-Peter Haring
    Landesnerven Klinik Wagner-Jauregg, Linz, Austria
  • Ingrid Stuiver
    Microislet, Inc., San Diego, California, U.S.A.
  • Simone Wagner
    Department of Neurology, University of Heidelberg, Heidelberg, Germany
  • Takeo Abumiya
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, U.S.A.
  • Jacinta Lucero
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, U.S.A.
  • Pauline Lee
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, U.S.A.
  • Brian R. Copeland
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, U.S.A.
  • Dietmar Seiffert
    Cardiovascular Research, 77 Dupont, Wilmington, Delaware, U.S.A.
  • Gregory J. del Zoppo
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, U.S.A.

抄録

<jats:p> The integrity of cerebral microvessels requires the close apposition of the endothelium to the astrocyte endfeet. Integrins α<jats:sub>1</jats:sub>β<jats:sub>1</jats:sub> and α<jats:sub>6</jats:sub>β<jats:sub>4</jats:sub> are cellular matrix receptors that may contribute to cerebral microvascular integrity. It has been hypothesized that focal ischemia alters integrin expression in a characteristic time-dependent manner consistent with neuron injury. The effects of middle cerebral artery occlusion (MCAO) and various periods of reperfusion on microvasclar integrin α<jats:sub>1</jats:sub>β<jats:sub>1</jats:sub> and α<jats:sub>6</jats:sub>β<jats:sub>4</jats:sub> expression were examined in the basal ganglia of 17 primates. Integrin subunits α<jats:sub>1</jats:sub> and β<jats:sub>1</jats:sub> colocalized with the endothelial cell antigen CD31 in nonischemic microvessels and with glial fibrillary acidic protein on astrocyte fibers. Rapid, simultaneous, and significant disappearance of both integrin α<jats:sub>1</jats:sub> and β<jats:sub>1</jats:sub> subunits and integrin α<jats:sub>6</jats:sub>β<jats:sub>4</jats:sub> occurred by 2 hours MCAO, which was greatest in the region of neuron injury (ischemic core, Ic), and progressively less in the peripheral (Ip) and nonischemic regions (N). Transcription of subunit β<jats:sub>1</jats:sub> mRNA on microvessels increased significantly in the Ic/Ip border and in multiple circular subregions within Ic. Microvascular integrin α<jats:sub>1</jats:sub>β<jats:sub>1</jats:sub> and integrin α<jats:sub>6</jats:sub>β<jats:sub>4</jats:sub> expression are rapidly and coordinately lost in Ic after MCAO. With loss of integrin α<jats:sub>1</jats:sub>β<jats:sub>1</jats:sub>, multiple regions of microvascular β<jats:sub>1</jats:sub> mRNA up-regulation within Ic suggest that microvessel responses to focal ischemia are dynamic, and that multiple cores, not a single core, are generated. These changes imply that microvascular integrity is modified in a heterogeneous, but ordered pattern. </jats:p>

収録刊行物

被引用文献 (6)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ