Therapeutic Hypothermia Influences Cell Genesis and Survival in the Rat Hippocampus following Global Ischemia
Therapeutic Hypothermia Influences Cell Genesis and Survival in the Rat Hippocampus following Global Ischemia
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DOI：
10.1038/jcbfm.2011.25
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发表时间：
2011-08
影响因子：
6.3
通讯作者：
G. Silasi;F. Colbourne
中科院分区：
文献类型：
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作者：
G. Silasi;F. Colbourne
延迟低温从全脑缺血损伤中挽救CA1神经元。然而，这种有效的神经保护剂对内源性修复机制的影响，如神经发生，还没有得到明确的研究。在这项研究中，我们对未经处理和低温处理的缺血后海马区新生成的细胞进行了量化和表型分析。我们首先证明了CA1区锥体神经元在缺血后不会自发再生。然后，我们比较了在缺血期间或之后开始降温时的神经保护水平。治疗效果随延迟时间的延长而下降，但延迟12小时的低温治疗具有神经保护作用。虽然在缺血组，溴脱氧尿苷(BrdU)的掺入增加，但由于BrdU标记没有与神经元核(Neun)共定位，因此没有发生CA1神经发生。相反，大多数BrdU标记的细胞是Iba阳性的小胶质细胞，神经保护性低温减少了缺血后第三周小胶质细胞的延迟生成。相反，延迟12小时的低温显著提高了缺血后4周新生齿状颗粒细胞的存活率。因此，我们的研究结果表明，CA1神经发生对低温神经保护没有贡献。重要的是，我们还表明，持续的低温与缺血后的修复过程有积极的相互作用，例如神经发生，从而改善功能结果。
Delayed hypothermia salvages CA1 neurons from global ischemic injury. However, the effects of this potent neuroprotectant on endogenous repair mechanisms, such as neurogenesis, have not been clearly examined. In this study, we quantified and phenotyped newly generated cells within the hippocampus following untreated and hypothermia-treated ischemia. We first show that CA1 pyramidal neurons did not spontaneously regenerate after ischemia. We then compared the level of neuroprotection when hypothermia was initiated either during or after ischemia. Treatment efficacy decreased with longer delays, but hypothermia delayed for up to 12 hours was neuroprotective. Although bromodeoxyuridine (BrdU) incorporation was elevated in ischemic groups, CA1 neurogenesis did not occur as the BrdU label did not colocalize with neuronal nuclei (NeuN) in any of the groups. Instead, the majority of BrdU-labeled cells were Iba-positive microglia, and neuroprotective hypothermia decreased the delayed generation of microglia during the third postischemic week. Conversely, hypothermia delayed for 12 hours significantly increased the survival of newly generated dentate granule cells at 4 weeks after ischemia. Thus, our findings show that CA1 neurogenesis does not contribute to hypothermic neuroprotection. Importantly, we also show that prolonged hypothermia positively interacts with postischemic repair processes, such as neurogenesis, resulting in improved functional outcome.