The effect of a dihydropyridine calcium antagonist (isradipine) on selective neuronal necrosis.
The experiments were designed to test the possibility that calcium influx into neurons via voltage sensitive calcium channels (VSCCs) contribute to brain damage in two conditions in which any amelioration of neuronal necrosis may be assumed not to occur through an improvement of blood flow, viz., hypoglycemic coma and brief transient ischemia. Hypoglycemic coma is thought to lead to neuronal necrosis by release of glutamate and cellular influx of calcium during the insult, while damage due to brief transient ischemia may, at least in part, result from increased calcium cycling across cell membranes in the postinsult period. The insults were delivered to anesthetized rats, and the localization and density of neuronal necrosis were evaluated by histopathology following 1 week of recovery. One dihydropyridine calcium antagonist (isradipine), given in doses which have been reported to ameliorate ischemic damage due to stroke, failed to reduce damage incurred by 30 min of hypoglycemic coma, or 15 min of transient forebrain ischemia. Provided that it can be assumed that isradipine in the doses employed reduced calcium influx via VSCCs, the results support the notion that calcium influx through VSCCs plays only a minor pathogenetic role in global/forebrain ischemia or in hypoglycemia, and they suggest that the effect of blockers of VSCCs in stroke, if any, is due to both blockade of VSCCs and increase in blood flow.
Ohta
S
S
Laboratory for Experimental Brain Research, University of Lund, Sweden.
Smith
M L
ML
Siesjö
B K
BK
D000818:Animals; D001927:Brain Diseases / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D002545:Brain Ischemia / Q000150:complications; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003128:Coma / Q000150:complications; D007003:Hypoglycemia / Q000150:complications; D017275:Isradipine; D008297:Male; D009336:Necrosis / Q000503:physiopathology; D009410:Nerve Degeneration / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D011725:Pyridines; D017275:Isradipine