Effects of Intracellular Calcium Reduction by Dantrolene on Prevention/Treatment of Ischemic Stroke.
BACKGROUND: It has been suggested that cerebral blood vessels and brain cells might depend more on intracellular calcium than extracellular calcium to modulate intracellular free calcium concentrations, [Ca(2+)](i). METHODS AND RESULTS: A potent intracellular calcium antagonist, dantrolene, was used to prevent the ischemic stroke induced in the rat model. It was found that treatment of rats with dantrolene at -1 hour and +1 hour after 60 minutes of ischemic insult prevented by the formation of cortical necrosis 98% and 85%, respectively. Further, the [Ca(2+)](i) of embryonic aorta cells was markedly reduced, and cAMP of the same cultured cells were significantly increased by dantrolene treatment. CONCLUSIONS: These results indicate that ischemic stroke is preventable by dantrolene through reduction of [Ca(2+)](i) and increase of cAMP.
Hong
SJ
Department of Pharmacology, Kaohsiung Medical College, Kaohsiung, Texas, Taiwan, ROC
Chiou
GC