Effect of glutamate on the cerebral microcirculation

William G. Mayhan, Sean P. Didion

Research output: Contribution to journalArticlepeer-review


Glutamate is an important excitatory neurotransmitter in the brain. While extracellular concentrations ol glutamate are normally low, brain injury has been shown to produce a significant increase in extracellular concentration of glutamate. The first goal of this study was to determine the effect of glutamate on the permeability of the blood-brain barrier and reactivity of cerebral arterioles. The second goal of this study w'as to determine a possible role for nitric oxide in the effects of glutamate on the cerebral microcirculation. We examined the pial microcirculation in rats using intravital microscopy. Permeability of the bloodbrain barrier (clearance of HTC-dextran- 10K) and diameter of pial arterioles were measured before and during application of glutamate in the absence and presence of L-NMMA (10 μM). ( Inder control conditions, clearance of FITC-dextran-lOK from pial vessels was minimal (0.78±0.1 ml/sec x 10-6) and diameter of pial artcnoles (51±4 μm) remained constant. lopical application of glutamate (0.1 and 1.0mM ) produced a dose-related increase in the clearance of FITC-dextran-lOK (1.7±0.5 and 2.1±0.3 ml/sec × 10-6. respectively) and diameter of pial arterioles ( 14±4 and 18±4%. respectively). L-NMMA significantly attenuated clearance of HTC-dextran-10K. and dilation of pial arterioles in response to glutamate. The findings of the present study suggest that glutamate, a major neurotransmitter in the brain, increases permeability of the blood-brain barrier to small molecules and dilates cerebral arterioles via a nitric oxide-dependent mechanism. We suggest that the release of glutamate during trauma to the brain may play an important role in regulating thu transport of molecules across the blood-brain barrier.

Original languageEnglish (US)
Pages (from-to)A31
JournalFASEB Journal
Issue number3
StatePublished - 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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