Survival and histological evaluation of therapeutic window of post-ischemia treatment with magnesium sulfate in embolic stroke model of rat.
The neuroprotective window of magnesium for up to 8 h after ischemic insult was evaluated in a clinically relevant model of focal cerebral ischemia subjected to embolization of the right middle cerebral artery (MCA) with an autologous thrombus. The animals were treated with either vehicle or 5% magnesium sulfate (90 mg/kg) intravenously at 2, or 6, or 8 h after ischemic insult. Survival rate significantly increased only in animals treated with magnesium sulfate in treatment groups at 2 h after MCA embolization but improvement in neurological outcome was observed in all medicated groups. Compared with animals in control group, post-ischemia treatment with magnesium sulfate significantly reduced brain infarct volume (P<0.01) except the 8 h group. These data indicate that the therapeutic window for neuroprotection of magnesium can be extended up to 6 h in the focal cerebral ischemia model of this study. The long window of opportunity for effective dosing may be explained with the proposed multiple mechanisms of actions for magnesium.
Yang
Y
Y
Department of Medicine (Neurology), University of Alberta, Edmonton, Alberta, Canada.
Li
Q
Q
Ahmad
F
F
Shuaib
A
A
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000401:mortality*; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D020766:Intracranial Embolism / Q000188:drug therapy / Q000401:mortality*; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000188:drug therapy / Q000401:mortality*; D015996:Survival Rate; D013997:Time Factors
D008278:Magnesium Sulfate