title: Regional and time-dependent neuroprotective effect of hypothermia following oxygen-glucose deprivation.
abstract: The neuroprotective effect of hypothermia has been demonstrated in in vivo and in vitro models of cerebral ischemia. In regard to the hippocampus, previous studies have mainly focused on CA1 pyramidal neurons, which are very vulnerable to ischemia. But the dentate gyrus (DG), in which neuronal proliferation occurs, can also be damaged by ischemia. In this study, we explored the neuroprotective effect of postischemic hypothermia in different areas of the hippocampus after mild or severe ischemia. Organotypic hippocampal slice cultures were prepared from 6- to 8-day-old rats and maintained for 12 days. Cultures were exposed to 25 or 35 min of oxygen and glucose deprivation (OGD). Neuronal damage was quantified after 6, 24, 48, and 72 h by propidium iodide fluorescence. Mild hypothermia (33°C) was induced 1 h after the end of OGD and was maintained for a period of 24 h. Short OGD produced delayed neuronal damage in the CA1 area and in the DG and to a lesser extend in the CA3 area. Damage in CA1 pyramidal cells was totally prevented by hypothermia whereas neuroprotection was limited in the DG. Thirty-five-minute OGD induced more rapid and more severe cell death in the three regions. In this case, hypothermia induced 1 h after OGD was unable to protect CA1 pyramidal cells whereas hypothermia induced during OGD was able to prevent cell loss. This study provides evidence that neuroprotection by hypothermia is limited to specific areas and depends on the severity of the ischemia.
authors.affiliation: Department of Neurosciences, Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium.
authors.forename: Justine
authors.initials: J
authors.lastname: Allard
authors.forename: Paula
authors.initials: P
authors.lastname: Paci
authors.forename: Luce
authors.initials: L
authors.lastname: Vander Elst
authors.forename: Laurence
authors.initials: L
authors.lastname: Ris
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology*; D007036:Hypothermia, Induced; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D020925:Hypoxia-Ischemia, Brain; D009474:Neurons / Q000473:pathology / Q000502:physiology; D066244:Proton Magnetic Resonance Spectroscopy; D017208:Rats, Wistar; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D005947:Glucose
keywords: hippocampus; in vitro; ischemia; organotypic