Glutamate microinjections in cerebellar cortex reproduce
cerebrovascular effects of parallel fiber stimulation.
Yang, Guang, and Costantino Iadecola.
Laboratory of Cerebrovascular Biology and Stroke, University of
Minnesota Medical School, Minneapolis, MN 55455
APStracts 3:0240R, 1996.
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 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 Na++ channel blocker tetrodotoxin (10 [mu]M;
-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
Mg++ and 0 mM Ca++ (-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, i.p)
reduced the flow response evoked by microinjection of glutamate (
-46+/-7%; n=5; p<0.05), but not acetylcholine (10 [mu]M;
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 are mediated by
glutamate release and activation of glutamate receptors. The data
also strengthens the hypothesis that glutamate and NO are important
mediators in the mechanisms linking synaptic activity to BFcrb in
cerebellar cortex.
Received 15 March 1996; accepted in final form 10 June 1996.
APS Manuscript Number R161-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96