Pastukhov Artem, Borisova Tatiana
Department of Neurochemistry, Palladin Institute of Biochemistry , National Academy of Sciences of Ukraine, Kiev, Ukraine .
Ther Hypothermia Temp Manag. 2018 Sep;8(3):143-149. doi: 10.1089/ther.2017.0047. Epub 2018 Feb 8.
Deep and profound hypothermia is successfully practiced in the prevention of ischemic stroke consequences and aortic arch cardiac surgery accompanied by reduction of cerebral circulation. Hypothermia is a current neuroprotection standard in hypoxic/ischemic encephalopathy. Drug-hypothermia administration is proposed as a new approach in pharmacotherapy for neonatal seizures. Also, hypothermia is useful as neuroprotective approach in long-term interplanetary space missions. We recently revealed gradual dynamics of hypothermia-induced decrease in transporter-mediated release and uptake of L-[C]glutamate in presynaptic rat brain nerve terminals (synaptosomes), thereby confirming potent unspecific neuroprotective effect of hypothermia. Glutamate homo- and heteroexchange are significant mechanisms involved in the maintenance of the extracellular glutamate level in nerve terminals. We have analyzed whether glutamate homo- and heteroexchange in nerve terminals is temperature sensitive. In this study we showed that synaptosomal glutamate-induced L-[C]glutamate release (homoexchange) and D-aspartate- and DL-threo-β-hydroxyaspartate-induced L-[C]glutamate release (heteroexchange) gradually decreased from deep (27°C) to profound (17°C) hypothermia with dynamics similar to that of glutamate transporter reversal. Interestingly, ambient L-[C]glutamate concentration in the nerve terminal preparations remained unaltered during hypothermia administration. Therefore, we demonstrated that glutamate homo- and heteroexchange decreased from deep to profound hypothermia thereby preventing further elevation of extracellular glutamate. Hypothermia uncovered the principal processes contributing to glutamate homo- and heteroexchange in nerve terminals and the maintenance of definite ambient glutamate concentration. Additionally, we showed that glutamate transporter reversal can be nonpathological and occurs under physiological conditions at least as a part of homo- and heteroexchange mechanisms.
深度和极深度低温已成功应用于预防缺血性中风后果以及伴有脑循环减少的主动脉弓心脏手术。低温是目前缺氧/缺血性脑病的神经保护标准。药物低温给药被提议作为新生儿癫痫药物治疗的一种新方法。此外，低温在长期星际太空任务中作为神经保护方法也很有用。我们最近揭示了低温诱导的大鼠突触前脑神经末梢（突触体）中转运体介导的L-[C]谷氨酸释放和摄取减少的渐进动态变化，从而证实了低温具有强大的非特异性神经保护作用。谷氨酸的同向和反向交换是维持神经末梢细胞外谷氨酸水平的重要机制。我们分析了神经末梢中谷氨酸的同向和反向交换是否对温度敏感。在这项研究中，我们表明，突触体谷氨酸诱导的L-[C]谷氨酸释放（同向交换）以及D-天冬氨酸和DL-苏式-β-羟基天冬氨酸诱导的L-[C]谷氨酸释放（反向交换）随着温度从深度低温（27°C）降至极深度低温（17°C）而逐渐减少，其动态变化与谷氨酸转运体逆转相似。有趣的是，在低温给药期间，神经末梢制剂中的环境L-[C]谷氨酸浓度保持不变。因此，我们证明了谷氨酸的同向和反向交换从深度低温到极深度低温逐渐减少，从而防止细胞外谷氨酸进一步升高。低温揭示了神经末梢中谷氨酸同向和反向交换以及维持特定环境谷氨酸浓度的主要过程。此外，我们表明谷氨酸转运体逆转可能是非病理性的，并且至少作为同向和反向交换机制的一部分在生理条件下发生。
