Blood flow-dependent functional recovery in a rat model of focal cerebral ischemia.
The reduction in focal infarct volume after L-arginine has been attributed to an increase in regional cerebral blood flow (rCBF) within ischemic tissue. We tested the hypothesis that L-arginine-induced rCBF increases precede the recovery of spontaneous electrical activity [electrocorticogram (ECoG)] in spontaneously hypertensive rats subjected to middle cerebral artery (MCA) occlusion. ECoG was recorded from the penumbral region of parietal cortex by a glass microelectrode inserted into 1-mm3 cortical tissue from which blood flow was sampled by laser-Doppler flowmetry. rCBF dropped to 21 +/- 8% of the preischemic level, and ECoG was depressed by 64 +/- 13% after distal MCA occlusion. L-Arginine infusion (300 mg/kg i.v.) increased rCBF in 14 out of 18 rats, and ECoG significantly recovered in seven rats in which rCBF exceeded 31% of preischemic flow. Increases in rCBF anticipated the functional improvement in every case. Saline (n = 6) or D-arginine (n = 5) administration was ineffective. These data demonstrate that increasing rCBF can promote functional recovery in the ischemic brain and suggest that early administration of L-arginine or other vasodilators may enhance tissue survival by increasing rCBF.
Dalkara
T
T
Stroke Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Morikawa
E
E
Panahian
N
N
Moskowitz
M A
MA
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002545:Brain Ischemia / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004562:Electrocardiography; D051381:Rats; D011918:Rats, Inbred SHR; D012965:Sodium Chloride / Q000494:pharmacology
D012965:Sodium Chloride; D001120:Arginine