N-methyl-D-aspartate induces cortical hyperemia through cortical spreading depression-dependent and -independent mechanisms in rats.
OBJECTIVE
N-methyl-d-aspartate (NMDA) is a powerful cerebrovascular dilator in vivo. Cortical spreading depression (CSD) has recently been shown to contribute to the pial arteriolar dilation in mice. Our main aim was to examine the participation of CSD in the overall cerebrovascular response to NMDA in the rat.


METHODS
Anesthetized Wistar rats (eight weeks old) were equipped with a closed cranial window to allow topical application of NMDA (10(-5)-10(-3) M) to the parietal cortex. Cortical blood flow (CoBF) under and outside the cranial window was simultaneously monitored by using a two-channel laser-Doppler flowmeter. CSDs were detected by recording the changes in the cortical DC potential.


RESULTS
Concentrations of 10(-4) and 10(-3) M of NMDA evoked single CSDs associated with rapid, transient hyperemia, followed by a sustained, but reduced, increase in CoBF. The latency and magnitude of the CoBF responses were dose dependent. The higher dose resulted in shorter latency (100+/-5* vs. 146+/-11 seconds, *P<0.05; mean+/-standard error of the mean) and larger overall flow response (77+/-12* vs. 28+/-3% from baseline) under, but not outside, the cranial window.


CONCLUSIONS
NMDA elicits dose-dependent increases in CoBF that are composed of CSD-dependent and -independent components in rats.
Lenti
Laura
L
Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA. lentilaura@gmail.com
Domoki
Ferenc
F
Gáspár
Tamás
T
Snipes
James A
JA
Bari
Ferenc
F
Busija
David W
DW
D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply*; D002560:Cerebrovascular Circulation; D013181:Cortical Spreading Depression / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006940:Hyperemia / Q000139:chemically induced*; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow
D016202:N-Methylaspartate