Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter

Masafumi Ihara, Hidekazu Tomimoto, Makoto Kinoshita, Jun Seo Oh, Makoto Noda, Hideaki Wakita, Ichiro Akiguchi, Hiroshi Shibasaki

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81 Citations (Scopus)

Abstract

White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white matter in a rat model of chronic cerebral hypoperfusion. After bilateral clipping of the common carotid arteries, myelin staining revealed demyelinating changes in the optic tract and the corpus callosum on day 7. Zymographic analyses indicated an increase in the level of MMP-2, but not MMP-9, after the hypoperfusion. Immunohistochemical analyses revealed the presence (most abundantly on day 3) of MMP-2-expressing activated microglia in the optic tract and corpus callosum. In contrast, the capillary endothelial cells expressed MMP-2 later. IgM-immunoreactive glial cells were absent in the sham-operated animals, but were present in the hypoperfused animals by day 3, reflecting the disrupted blood-brain barrier. These findings suggest that the main sources of the elevated MMP-2 were the microglia and the endothelium, and that these cells may contribute to the remodeling of the white matter myelin and microvascular beds in chronic cerebral hypoperfusion.

Original languageEnglish
Pages (from-to)828-834
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume21
Issue number7
Publication statusPublished - 2001 Jul 16
Externally publishedYes

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Keywords

  • Chronic cerebral hypoperfusion
  • Demyelination
  • Matrix metalloproteinase
  • Microglia
  • Rat
  • White matter lesions

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

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