A selective N-type Ca(2+)-channel blocker prevents CA1 injury 24 h following severe forebrain ischemia and reduces infarction following focal ischemia.

Journal article

SNX-111 (NEUREX Corporation, Menlo Park, CA, U.S.A.) an omega-conopeptide, was tested for cytoprotection following normothermic ischemia using both a four-vessel occlusion model of severe forebrain ischemia and a model of transient middle cerebral artery occlusion focal ischemia. Adult male Wistar rats were subjected to 10 min of forebrain ischemia followed by 7 days of reperfusion. A single dose of SNX-111 (5 mg/kg) was injected intravenously following delays of either 6 or 24 h after reperfusion. For 11 rats treated with saline, there was 78 +/- 13% CA1 neuronal injury (mean +/- SD); for 11 given SNX-111 delayed by 6 h, injury was reduced to 35 +/- 30% (p < 0.01); and remarkably, treatment delayed by 24 h (n = 10), still resulted in protection, with only 50 +/- 29% injury (p < 0.05). Adult male spontaneously hypertensive rats had transient occlusion of the right middle cerebral artery of 1.5- or 2-h duration followed by 22.5 or 22 h of reperfusion, respectively. Rats were randomly assigned to receive either saline or SNX-111 (5 mg/kg i.v.), with treatment starting immediately after reperfusion (1.5-h ischemic group) or at 1 h following the onset of ischemia (2-h ischemic group). In the 1.5-h ischemic group, saline-treated animals sustained 138 +/- 32 mm3 of neocortical infarction (n = 9), and SNX-111 treatment resulted in an infarct reduction to 76 +/- 25 mm3 (n = 9; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Authors: Buchan, A; Gertler, S; Li, H; Xue, D; Huang, Z

• Publication status: Published
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
• Volume: 14
• Issue: 6
• Pages: 903-910
• Publication date: 1994-11-01
• DOI: 10.1038/jcbfm.1994.121
• EISSN: 1559-7016
• ISSN: 0271-678X
• Language: English
• Keywords: Rats, Inbred SHR; Animals; omega-Conotoxins; Survival Analysis; Hippocampus; Peptides; Calcium Channel Blockers; Morbidity; Rats; Cerebral Infarction; Prosencephalon; Cerebrovascular Circulation; Male; Rats, Wistar; Brain Ischemia