Delayed and prolonged post-ischemic hypothermia is neuroprotective in the gerbil.
Global ischemia, in the gerbil, produces profound hippocampal CA1 loss which leads to functional abnormalities (e.g. habituation impairment). In experiment 1, gerbils were subjected to 3 or 5 min of normothermic (brain) ischemia. Hypothermic groups were cooled to 32 degrees C for 12 h beginning 1 h after ischemia, while control groups (no hypothermia) regulated their own temperature. Exploration in a novel open field was assessed on days 3, 7 and 10 following ischemia and CA1 neurons were counted after 10- or 30-day survival. Both ischemia durations produced severe CA1 necrosis which resulted in increased open field activity. Hypothermia attenuated this behavioral pattern and substantially reduced CA1 necrosis against 3 min of ischemia when assessed at 10 and 30 days, but was only partially effective against a 5 min occlusion where, in addition, some cell death appeared to be delayed rather than prevented. In experiment 2, gerbils were occluded for 5 min and survived for 30 days. Twenty-four hours of hypothermia initiated 1 h after ischemia resulted in near total preservation of CA1 neurons. Thus, increasing the duration of post-ischemic hypothermia from 12 to 24 h produced much greater neuroprotection against severe ischemia. Prolonged post-ischemic hypothermia may be a valuable intervention in stroke patients.
Colbourne
F
F
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Corbett
D
D
D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature; D005106:Exploratory Behavior; D005260:Female; D005849:Gerbillinae; D006624:Hippocampus / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D007036:Hypothermia, Induced; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009336:Necrosis; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D017966:Pyramidal Cells / Q000473:pathology / Q000502:physiology*; D012016:Reference Values; D013997:Time Factors