Sexually dimorphic response of TRPM2 inhibition following cardiac arrest-induced global cerebral ischemia in mice.
Sexually dimorphic response of TRPM2 inhibition following cardiac arrest-induced global cerebral ischemia in mice.
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DOI：
10.1007/s12031-013-0005-9
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Herson PS
中科院分区：
文献类型：
--
作者：
Nakayama S;Vest R;Traystman RJ;Herson PS
由心脏骤停后复苏（CA/CPR）引起的短暂性全脑缺血在脑内脆弱的神经元群体（例如海马CA 1神经元）中引起显著的神经损伤。近年来，瞬时受体电位M2（TRPM 2）通道被认为是神经元缺血性损伤的介导者。我们以前证明，减少TRPM 2功能的遗传和药理学策略优先保护体外雄性神经元，并减少实验性中风后的梗死体积。由于缺血性卒中后干预的治疗窗较窄，因此评估TRPM 2在其他脑缺血模型中的作用非常重要。因此，本研究利用改良的心脏骤停和心肺复苏（CA/CPR）小鼠模型，通过始终保持身体和头部温度接近生理范围，更准确地模拟临床状况。在这里，我们报告，TRPM 2活性抑制克霉唑（CTZ）减少海马CA 1神经元损伤时，从心脏骤停复苏后30分钟给药。与我们之前的观察结果一致，在雄性小鼠中观察到神经保护作用，在雌性小鼠中未观察到对损伤的影响。这些发现为TRPM 2作为男性大脑中脑缺血保护的靶点提供了进一步的证据。
Transient global cerebral ischemia due to cardiac arrest followed by resuscitation (CA/CPR) causes significant neurological damage in vulnerable neuron populations within the brain, such as hippocampal CA1 neurons. In recent years, we have implicated the transient receptor potential M2 (TRPM2) channel as a mediator of ischemic injury to neurons. We previously demonstrated that genetic and pharmacological strategies that reduce TRPM2 function preferentially protect male neurons in vitro and reduce infarct volume following experimental stroke. Due to the narrow therapeutic window for intervention following ischemic stroke, it is important to assess the role of TRPM2 in other models of cerebral ischemia. Therefore, this study utilized a modified mouse model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR) to mimic more accurately the clinical condition by maintaining body and head temperatures near the physiological range throughout. Here we report that inhibition of TRPM2 activity with clotrimazole (CTZ) reduces hippocampal CA1 neuronal injury when administered 30 minutes after resuscitation from cardiac arrest. Consistent with our previous observations, neuroprotection was observed in male mice and no effect on injury was observed in the female. These findings provide further evidence for TRPM2 as a target for protection against cerebral ischemia in the male brain.
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影响因子：
7.3
作者：
Fonfria, E;Marshall, ICB;McNulty, S
通讯作者：
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影响因子：
3
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影响因子：
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通讯作者：
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