Efficacious experimental stroke treatment with high-dose methylprednisolone

Abstract

Background and purpose: Recent studies reveal success in treating spinal cord trauma with early, high-dose methylprednisolone. As in spinal cord research, failure to find therapeutic effects with steroids in studies of acute stroke treatment may reflect institution of treatment too late and at too low dosage. We presently test the efficacy of stroke treatment with methylprednisolone administered early and at high doses using a cat temporary middle cerebral artery occlusion model.

Methods: We occluded the middle cerebral artery for 4 hours in 24 pentobarbital-anesthetized cats. To enhance the probability of brain injury, we maintained the cats' serum glucose concentrations at high levels both during 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 with vehicle. During and for 8 hours after occlusion, we monitored cerebral blood flow, brain and rectal temperatures, and multiple cardiovascular and blood compositional parameters. We assessed brain pathological outcome after animal survival for 4 days or after acute death from hemispheric edema.

Results: Experimental and control animals showed similar early mortality rates (treated, 3/12; controls, 4/12). However, surviving methylprednisolone-treated cats (n = 9) showed a mean infarct size more than six times smaller than in the control animals (n = 8) (mean +/- SEM, 2.4 +/- 0.7% versus 15.6 +/- 6.2% of the ischemic territory, respectively; P < .05). The methylprednisolone-treated animals also showed less marked reduction in cerebral blood flow during ischemia than did the controls (mean +/- SEM, 58 +/- 5% versus 74 +/- 4%; P < .005).

Conclusions: Administering methylprednisolone at high doses early after onset of ischemia significantly reduces tissue injury in cats that survive 4 days of temporary middle cerebral artery occlusion. This improvement in outcome occurs in the setting of significant increases in ischemic cerebral blood flow. However, methylprednisolone treatment did not reduce hemispheric edema in animals that died early after temporary middle cerebral artery occlusion.