The effects of a competitive NMDA receptor antagonist (CGS-19755) on cerebral blood flow and pH in focal ischemia.
We report the effects of intravenous infusion of CGS-19755, a potent competitive N-methyl-D-aspartate (NMDA) antagonist, on local cerebral pH (LCpH) and local CBF (LCBF) in rats with occluded left middle cerebral and common carotid arteries. LCpH and LCBF were determined simultaneously by a double-label autoradiographic technique 4 h after vascular occlusion in three groups: no treatment, carrier infused, and a group receiving CGS-19755 at 10 mg/kg bolus immediately after occlusion followed by infusion at 5 mg kg-1 h-1 for 4 h. Compared with rats receiving carrier, several cortical structures on the side of occlusions showed significantly higher CBF in rats receiving CGS-19755. This drug also corrected the pH in several left cortical structures to values significantly higher than in the rats receiving carrier. The correction in LCpH was not limited to those regions showing significant elevations in LCBF. In the nonoccluded hemisphere, CGS-19755 significantly increased the hemispheric mean blood flow from 122 +/- 17 to 221 +/- 64 ml 100 g-1 min-1 (mean +/- SD of all structures, p less than 0.01) without any changes in LCpH. Cortical but not basal ganglia infarct volume was significantly smaller in rats receiving CGS-19755 than in the carrier-treated group. These results suggest that, at least partially, the neuroprotective effect of CGS-19755 in ischemia may be related to changes in CBF and pH in addition to its antagonist effect on the NMDA receptor.
Takizawa
S
S
McConnell Brain Imaging Centre, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Hogan
M
M
Hakim
A M
AM
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010875:Pipecolic Acids / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; C053672:selfotel; D016202:N-Methylaspartate