N-methyl-D-aspartate increases cortical blood flow in part by evoking cortical spreading depression in Wistar, and insulin resistant Zucker rats
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1
Department of Physiology, University of Szeged, Hungary
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2
Department of Physiology & Pharmacology, Wake Forest University Health Sciences, United States
NMDA dilates pial arterioles via evoking cortical spreading depression (CSD) in mice; however, a dose-dependent action was described in piglets. The mechanism of the cerebral vascular response in rats is unclear. The purpose of our study was to critically examine the effect of NMDA on the cortical blood flow (CoBF) in this model. Further, we sought to determine whether this microvascular response is reduced in the Zucker obese rats, since insulin resistance (IR) impairs vascular reactivity of large cerebral arteries. Anesthetized, ventilated Wistar (8 weeks old), Zucker obese and lean (12 weeks old, n=8-8) rats were equipped with closed cranial window. NMDA (10-4 10-3 M) was applied to the parietal cortex, while CoBF (using Laser-Doppler flowmetry) and cortical DC potential were monitored. NMDA evoked CSD at both concentrations in all experimental groups. After a rapid, transient hyperemia, sustained increases in CoBF were observed. The latency and peak amplitude of the CoBF response to CSD was dose-related: the higher dose resulted in shorter latency (100±5* vs. 146±11 s, all data from Wistars, *p<0.05) and larger amplitude (237±45* vs. 168±34, % of baseline). The sustained CoBF elevation after the CSD was also dose-dependent: 51±10* vs. 19±4% (average of 2-6th minutes after the peak values). CoBF responses were similar in lean and obese rats. In conclusion, the cerebrovascular response to NMDA in rats is partially due to CSDs. The unchanged CoBF response to NMDA/CSD in Zucker obese rats indicates that the microvascular response to this stimulus remains intact in IR.
Supported by OTKA (K63401 and IN69967)
Conference:
12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009.
Presentation Type:
Poster Presentation
Topic:
Pathophysiology and neurology - degenerative disorders
Citation:
Lenti
L,
Domoki
F,
Busija
DW and
Bari
F
(2009). N-methyl-D-aspartate increases cortical blood flow in part by evoking cortical spreading depression in Wistar, and insulin resistant Zucker rats.
Front. Syst. Neurosci.
Conference Abstract:
12th Meeting of the Hungarian Neuroscience Society.
doi: 10.3389/conf.neuro.01.2009.04.162
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Received:
05 Mar 2009;
Published Online:
05 Mar 2009.
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Correspondence:
Laura Lenti, Department of Physiology, University of Szeged, Szeged, Hungary, lauralenti@yahoo.com