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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Characterization of neuroprotection from excitotoxicity by moderate and profound hypothermia in cultured cortical neurons unmasks a temperature-insensitive component of glutamate neurotoxicity.
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Characterization of neuroprotection from excitotoxicity by moderate and profound hypothermia in cultured cortical neurons unmasks a temperature-insensitive component of glutamate neurotoxicity.

机译：培养皮层神经元中度和深度低温对神经保护免受兴奋性毒性的特征，揭示了对温度不敏感的谷氨酸神经毒性成分。

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Although profound hypothermia has been used for decades to protect the human brain from hypoxic or ischemic insults, little is known about the underlying mechanism. We therefore report the first characterization of the effects of moderate (30 degrees C) and profound hypothermia (12 degrees to 20 degrees C) on excitotoxicity in cultured cortical neurons exposed to excitatory amino acids (EAA; glutamate, N-methyl-D-aspartate [NMDA], AMPA, or kainate) at different temperatures (12 degrees to 37 degrees C). Cooling neurons to 30 degrees C and 20 degrees C was neuroprotective, but cooling to 12 degrees C was toxic. The extent of protection depended on the temperature, the EAA receptor agonist employed, and the duration of the EAA challenge. Neurons challenged briefly (5 minutes) with all EAA were protected, as were neurons challenged for 60 minutes with NMDA, AMPA, or kainate. The protective effects of hypothermia (20 degrees and 30 degrees C) persisted after rewarming to 37 degrees C, but rewarming from 12 degrees C was deleterious. Surprisingly, however, prolonged (60 minutes) exposures to glutamate unmasked a temperature-insensitive component of glutamate neurotoxicity that was not seen with the other, synthetic EAA; this component was still mediated via NMDA receptors, not by ionotropic or metabotropic non-NMDA receptors. The temperature-insensitivity of glutamate toxicity was not explained by effects of hypothermia on EAA-evoked [Ca2+]i increases measured using high- and low-affinity Ca2+ indicators, nor by effects on mitochondrial production of reactive oxygen species. This first characterization of excitotoxicity at profoundly hypothermic temperatures reveals a previously unnoticed feature of glutamate neurotoxicity unseen with the other EAA, and also suggests that hypothermia protects the brain at the level of neurons by blocking, rather than slowing, excitotoxicity.
机译：尽管深低温疗法已被用于保护人类大脑免受缺氧或缺血性损伤数十年之久，但对其潜在机制知之甚少。因此，我们报告了中度（30摄氏度）和深低温（12摄氏度至20摄氏度）对暴露于兴奋性氨基酸（EAA;谷氨酸，N-甲基-D-天门冬氨酸）的皮质神经元兴奋毒性的影响的首次表征[NMDA]，AMPA或红藻氨酸盐）在不同的温度（12到37摄氏度）下使用。将神经元冷却至30摄氏度和20摄氏度具有神经保护作用，但冷却至12摄氏度则具有毒性。保护程度取决于温度，使用的EAA受体激动剂和EAA攻击的持续时间。所有EAA短暂攻击（5分钟）的神经元都受到保护，NMDA，AMPA或海藻酸盐攻击60分钟的神经元也受到保护。再度升至37度后，体温过低（20度和30度）的保护作用仍然存在，但从12度再度升高是有害的。然而，令人惊讶的是，长时间（60分钟）暴露于谷氨酸盐可以掩盖对谷氨酸神经毒性的温度不敏感成分，而其他合成的EAA则未见此现象。该成分仍是由NMDA受体介导的，而不是由离子型或代谢型非NMDA受体介导的。用高和低亲和力Ca2 +指示剂测得的低温对EAA诱发的[Ca2 +] i升高的影响，也不能通过对活性氧的线粒体产生的影响来解释谷氨酸毒性对温度的敏感性。在深低温下的兴奋性毒性的第一个特征揭示了谷氨酸神经毒性以前没有被人注意到的其他EAA所未见的特征，并且还暗示了低温通过阻止而不是减缓兴奋性毒性在神经元水平上保护大脑。

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