Glutamate-induced disruption of the blood-brain barrier in rats: Role of nitric oxide

William G. Mayhan, Sean P. Didion

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Background and Purpose: the first goal of this study was to determine the effect of glutamate on permeability and reactivity of the cerebral microcirculation. The second goal of this study was to determine a possible role for nitric oxide in the effects of glutamate on the cerebral microcirculation. Methods: We examined the pial microcirculation in rats with intravital microscopy. Permeability of the blood-brain dextran (molecular weight, 10 000 D; FITC-dextran-10K) before and during application of glutamate (0.1 and 1.0 mmol/L). In addition, we examined the permeability of the blood-brain barrier during application of a nitric oxide donor, S- nitroso-acetyl-penicillamine (SNAP; 10 μmol/L). Diameter of pial arterioles was measured before and during application of glutamate or SNAP. To determine a potential role for nitric oxide in glutamate-induced effects on the cerebral microcirculation, we examined the effects of N(G)-monomethyl-L- arginine (10 μmol/L). Results: In control rats, clearance of FITC-dextran- 10K from pial vessels was minimal, and the diameter of pial arterioles remained constant during the experimental period. Topical application of glutamate (0.1 and 1.0 mmol/L) and SNAP (10 μmol/L) produced an increase in clearance of FITC-dextran-10K and in diameter of pial arterioles. In addition, N(G)-monomethyl-L-arginine (10 μmol) attenuated glutamate-induced increases in permeability of the blood-brain barrier and glutamate-induced dilatation of cerebral arterioles. Conclusions: The findings of the present study suggest that glutamate, a major neurotransmitter in the brain, increases permeability of the blood-brain barrier to low-molecular-weight molecules and dilates cerebral arterioles via a nitric oxide-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)965-970
Number of pages6
JournalStroke
Volume27
Issue number5
DOIs
StatePublished - May 1996

Keywords

  • blood-brain barrier
  • cerebral circulation
  • glutamate
  • nitric oxide
  • rats

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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