AJP - Regulatory, Integrative and Comparative Physiology, Vol 271, Issue 6 1568-R1575, Copyright © 1996 by American Physiological Society

ARTICLES

Glutamate microinjections in cerebellar cortex reproduce cerebrovascular effects of parallel fiber stimulation

G. Yang and C. Iadecola
Laboratory of Cerebrovascular Biology and Stroke, University of Minnesota Medical School, Minneapolis 55455, USA.

Electrical stimulation of cerebellar parallel fibers releases glutamate and increases local blood flow (BFcrb), an effect in part mediated by glutamate-induced nitric oxide (NO) production. We studied whether local microinjection of glutamate into the cerebellar cortex would produce increases in BFcrb comparable to those elicited by parallel fiber stimulation. In halothane-anesthetized rats equipped with a cranial window, glutamate was microinjected into the cerebellar molecular layer, and BFcrb was monitored by laser-Doppler flowmetry. Glutamate microinjections increased BFcrb dose dependently (2-200 pmol in 200 nl) (n = 9) and by 55 +/- 6% at 200 pmol (mean +/- SE). The magnitude and temporal profile of the increases in BFcrb compared favorably with the increase in flow produced by parallel fiber stimulation. The glutamate-induced BFcrb increase was attenuated by superfusion with the Na2+ channel blocker tetrodotoxin (10 microM; -50 +/- 10%; n = 5; P < 0.05; t-test) or by blocking synaptic activity by treatment of the cerebellar cortex with Ringer containing 20 mM Mg2+ and 0 mM Ca2+ (-80 +/- 4%; n = 6; P < 0.05). The glutamate-receptor antagonist kynurenate (10 mM) attenuated the increase in BFcrb by 59 +/- 6% (P < 0.05; n = 5). The relatively selective inhibitor of neuronal NO synthase 7-nitroindazole (100 mg/kg ip) reduced the flow response evoked by microinjection of glutamate (-46 +/- 7%; n = 5; P < 0.05) but not acetylcholine (10 microM; P > 0.05; n = 6). We conclude that glutamate microinjections increase local BFcrb via activation of glutamate receptors. The glutamate-induced vasodilation is mediated, in part, by neurally derived NO. The striking similarities between the vascular responses evoked by parallel fiber stimulation and that produced by microinjection of glutamate support the hypothesis that the increase in BFcrb produced by parallel fiber stimulation is mediated by glutamate release and activation of glutamate receptors. The data also strengthen the hypothesis that glutamate and NO are important mediators in the mechanisms linking synaptic activity to BFcrb in cerebellar cortex.

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