Characterization of postischemic behavioral deficits in gerbils with and without hypothermic neuroprotection.
Five minutes of global ischemia in gerbil results in delayed hippocampal CA1 neuronal degeneration, which is accompanied by working memory impairments and hyperactivity in novel environments. In this study, postischemic activity was characterized in familiar and in novel environments to determine whether hyperactivity was due to impaired spatial habituation or another form of motor hyperactivity. This study also determined whether 6-h delayed hypothermia, which reduces CA1 neuronal injury, would attenuate functional impairments. Gerbils were subjected to 5 min of normothermic ischemia or sham operation 2 days following implantation of brain temperature probes. One of two ischemic groups was cooled (>48 h) starting at 6-h postischemia. Locomotor activity in a familiar cage was measured for 6 days while activity in three novel environments was intermittently measured on days 4, 5 and 6. Open field behavior and working memory in a T-maze were also assessed. Untreated ischemia caused marked hyperactivity in the familiar cage on day 1, which reverted to near-normal by day 2. Nonetheless, these gerbils showed hyperactivity during novel environment sessions on days 4-6. This maze behavior, which predicted hippocampal CA1 injury, was not due to different habituation rates nor baseline hyperactivity. Conversely, open field sessions on day 8 revealed ischemic habituation rate deficits. Ischemia also impaired working memory in the T-maze. Delayed hypothermia, which reduced neuronal loss in the CA1 sector to 12% from 81%, reduced all functional impairments. Ischemic gerbils quickly developed spontaneous locomotion hyperactivity that returned to near-normal after 1 day. This motor hyperactivity did not explain the elevated activity found with delayed testing in novel environments. Regardless, only the open field test on day 8 revealed a habituation-like deficit.
Colbourne
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F
Department of Pathology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, Canada. colbourn@acs.ucalgary.ca
Auer
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RN
Sutherland
G R
GR
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001831:Body Temperature; D001921:Brain / Q000098:blood supply / Q000502:physiology; D002545:Brain Ischemia / Q000503:physiopathology*; D002404:Catheterization; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005849:Gerbillinae / Q000502:physiology*; D006624:Hippocampus / Q000098:blood supply / Q000293:injuries / Q000502:physiology; D006948:Hyperkinesis; D007036:Hypothermia, Induced; D008124:Locomotion / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D013997:Time Factors