EFFICACIOUS EXPERIMENTAL STROKE TREATMENT WITH HIGH-DOSE METHYLPREDNISOLONE

Background and Purpose Recent studies reveal success in treating spina l cord trauma with early, high-dose methylprednisolone. As in spinal c ord research, failure to find therapeutic effects with steroids in stu dies of acute stroke treatment may reflect institution of treatment to o late and at too low dosage. We presently test the efficacy of stroke treatment with methylprednisolone administered early and at high dose s using a cat temporary middle cerebral artery occlusion model. Method s We occluded the middle cerebral artery for 4 hours in 24 pentobarbit al-anesthetized cats. To enhance the probability of brain injury, we m aintained the cats' serum glucose concentrations at high levels both d uring occlusion and for 6 hours afterward. Using a blinded, randomized study design, we treated 12 cats with methylprednisolone (30 mg/kg IV infused over 15 minutes starting 30 minutes after occlusion followed by 5.4 mg.kg(-1).h(-1) IV for the next 23 hours) and 12 control cats w ith vehicle. During and for 8 hours after occlusion, we monitored cere bral blood flow, brain and rectal temperatures, and multiple cardiovas cular and blood compositional parameters. We assessed brain pathologic al outcome after animal survival for 4 days or after acute death from hemispheric edema. Results Experimental and control animals showed sim ilar early mortality rates (treated, 3/12; controls, 4/12). However, s urviving methylprednisolone-treated cats (n=9) showed a mean infarct s ize more than six times smaller than in the control animals (n=8) (mea n+/-SEM, 2.4+/-0.7% versus 15.6+/-6.2% of the ischemic territory, resp ectively; P<.05), The methylprednisolone-treated animals also showed l ess marked reduction in cerebral blood flow during ischemia than did t he controls (mean+/-SEM, 58+/-5% versus 74+/-4%; P<.005). Conclusions Administering methylprednisolone at high doses early after onset of is chemia significantly reduces tissue injury in cats that survive 4 days of temporary middle cerebral artery occlusion. This improvement in ou tcome occurs in the setting of significant increases in ischemic cereb ral blood flow. However, methylprednisolone treatment did not reduce h emispheric edema in animals that died early after temporary middle cer ebral artery occlusion.