Sulfonylurea receptor 1 expression in human cerebral infarcts

Rupal I. Mehta, Svetlana Ivanova, Cigdem Tosun, Rudy J. Castellani, Volodymyr Gerzanich, J. Marc Simard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

In animal models of stroke, sulfonylurea receptor 1 (Sur1), a member of the adenosine triphosphate binding cassette transporter gene family, is transcriptionally upregulated in neural and vascular cells in which it plays a leading role in edema formation and necrotic cell death. To date, expression of Sur1 in the brains of humans with cerebral infarcts has not been systematically evaluated. We examined Sur1 expression in postmortem specimens obtained from 13 patients within the first 31 days after focal infarcts, 5 patients with lacunar infarcts, and 6 normal control brains using immunohistochemistry. Elevated immunoreactivity for Sur1 was detected in all cases of focal infarcts, with 3 distinct temporal patterns of expression: 1) neurons and endothelium showed the greatest elevation during the first week, after which levels declined; 2) astrocytes and microglia/macrophages showed progressive increases during the first 31 days; and 3) neutrophils near the infarct showed prominent immunoreactivity that did not change over time. Upregulation of Sur1 was corroborated using in situ hybridization for Abcc8 mRNA. Sulfonylurea receptor 1 immunoreactivity in lacunar infarcts was less prominent and more sporadic than in nonlacunar infarcts. In conjunction with previous studies, these data suggest that Sur1 may be a promising treatment target in patients with acute cerebral infarction.

Original languageEnglish (US)
Pages (from-to)871-883
Number of pages13
JournalJournal of neuropathology and experimental neurology
Volume72
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

Keywords

  • Astrocytes
  • Endothelium
  • Ischemic stroke
  • Lacunar infarct
  • Macrophages
  • Microglia
  • Neurons
  • Sulfonylurea receptor 1
  • Sur1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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