title: 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.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Sir Charles Gairdner Hospital, Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Australian Neuromuscular Research Institute, Australia.
authors.forename: Hongdong
authors.initials: H
authors.lastname: Zhu
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Meloni
authors.forename: Christina
authors.initials: C
authors.lastname: Bojarski
authors.forename: Michael W
authors.initials: MW
authors.lastname: Knuckey
authors.forename: Neville W
authors.initials: NW
authors.lastname: Knuckey
mesh_terms: 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
chemical_list: D002121:Calcium Channel Blockers; D008278:Magnesium Sulfate