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.