Post-ischemic modest hypothermia (35 degrees C) combined with intravenous magnesium is more effective at reducing CA1 neuronal death than either treatment used alone following global cerebral ischemia in rats.
In this study, we investigated the efficacy of pre- and 2 h post-ischemic magnesium treatment with different durations of modest hypothermia (35 degrees C) induced immediately or 2 h following global cerebral ischemia in rats. In experimental group 1, rats received an intravenous loading dose (LD) of 360 micromol/kg MgSO4 immediately before ischemia followed by a 48 h intravenous infusion (IVI) at 120 micromol/kg/h. Immediately post-ischemia, body temperature was lowered to 35 degrees C for 6 h or maintained at 37 degrees C. In experimental group 2, 2 h after ischemia, rats received the MgSO4 LD/IVI and/or had their body temperature lowered to 35 degrees C for 6, 12 or 24 h. In experimental group 1, ischemic rats receiving 6 h of modest hypothermia demonstrated 9.4% CA1 neuronal survival, whereas rats treated with magnesium alone or magnesium and 6 h of modest hypothermia demonstrated 5.1% and 37.9% neuronal survival, respectively. In experimental group 2, ischemic rats receiving 6, 12 or 24 h of modest hypothermia demonstrated 6.1, 5 and 43% CA1 neuronal survival, respectively. Rats treated with magnesium and 6, 12 or 24 h of modest hypothermia demonstrated 8.1, 9 and 76% neuronal survival, respectively. Our findings demonstrate that post-ischemic treatment with a 24 h duration of modest hypothermia and magnesium is more effective than either treatment used alone.
Zhu
Hongdong
H
Department of Neurosurgery, Sir Charles Gairdner Hospital, Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Australian Neuromuscular Research Institute, Australia.
Meloni
Bruno P
BP
Bojarski
Christina
C
Knuckey
Michael W
MW
Knuckey
Neville W
NW
D000818:Animals; D001831:Body Temperature / Q000502:physiology; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000166:cytology; D007035:Hypothermia; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000628:therapy*; D007275:Injections, Intravenous / Q000379:methods; D008278:Magnesium Sulfate / Q000008:administration & dosage*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D013997:Time Factors
D002121:Calcium Channel Blockers; D008278:Magnesium Sulfate