The Effects Of Delayed Hypothermia On Functional Recovery And Neurogenesls After Ischemia-Reperfusion Brain Injury In Rat

Background and Purpose:In contrast to intra-ischemic mild or moderate hypothermia, relatively little is known about the protective mechanisms of delayed post-ischemic hypothermia against stroke. This study investigates whether a delayed hypothermia, which does not reduce infarct size, improves neurological function and stroke-induced neurogenesis.Methods:Delayed hypothermia was induced by reducing the core temperature of rats to 30℃ at 15 minutes after 1-hour transient focal ischemia and maintained for 3 hours. We used behavioral tests, bromodeoxyuridine (BrdU) labeling, and cell lineage analysis with confocal microscopy to determine functional recovery and neurogenesis.Results:Delayed hypothermia did not reduce infarction but improved functional outcomes. In contrast to normothermia, delayed hypothermia increased BrdU+ cell numbers measured at 3 hours in the ipsilateral subventricular zone (SVZ) with a single pulse of BrdU. For rats receiving BrdU labeling 7 consecutive days after stroke, the accumulated BrdU+ cell numbers increased at 7 and 14 days in the ipsilateral SVZ of the hypothermic but not the normothermic brain; however, cell numbers increased at 7 days but decreased at 14 days in the ipsilateral dentate gyrus, and did not change in the peri-infarct region. Additionally, hypothermia increased the fraction of BrdU+ cells co-labeled with doublecortin, Nestin, NeuN, glial fibrillary acidic protein, or NG2 at some post-ischemic time points.Conclusions:Delayed hypothermia may prevent ischemic damage and improve functional outcomes in part by enhancing cell proliferation or altering the fate of newborn cells following stroke.