Use of diffusion-weighted MRI and neurological deficit scores to demonstrate beneficial effects of isradipine in a rat model of focal ischemia.
The neuroprotective effects of isradipine, a 2,4-dihydropyridine calcium channel blocker, has been well studied in the rat model of focal ischemia (induced by middle cerebral artery occlusion, MCAO). The present study was designed to evaluate whether isradipine pretreatment caused early (0-3 h after stroke) ischemic changes in diffusion- weighted magnetic resonance imaging (DWI) and if such changes were predictive of previously documented protection in brain infarction. An initial dose-response study using neurological deficit scores and estimates of protection from brain infarction (by histology) showed that isradipine reduced cortical infarctions compared to vehicle-treated animals at most doses (between 1.25 and 5 mg/kg/day s.c. for 6 days) with the best results obtained at 5 mg/kg/day, where a 78.5% reduction was observed. This dose was utilized to perform the DWI study. Early quantitative estimates of infarct size, as measured by DWI at 1, 2 and 3 h after MCAO, were similar to those obtained with late histology at 24 h. These data indicate that in pretreatment protocols, DWI can be used to quantitatively predict areas at risk of permanent damage. This work also demonstrates that neurological deficits, developing from the damaged forebrain following focal stroke, may provide an index of isradipine's neuroprotective activity.
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D017275:Isradipine / Q000008:administration & dosage / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009422:Nervous System Diseases / Q000145:classification*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR