Development of neuroprotection approaches for long-term space missions

Abstract

The study aimed to develop a strategy and methodology for neuroprotection during long-term space missions, which is based on a comprehensive study of the impact of therapeutic hypothermia combined with the action of neuroactive drugs on the key characteristics of synaptic transmission in brain nerve terminals, which change under the influence of planetary dust and conditions of altered gravity. Development of neurotoxicity under conditions of altered gravity may result from excess extracellular glutamate caused by the reverse functioning of glutamate transporters. Under conditions of moderate and deep hypothermia, a gradual decrease in the transporter-mediated release of L-[14C]glutamate from nerve terminals was demonstrated, which is stimulated by plasma membrane depolarization with KCl and dissipation of the proton gradient of synaptic vesicles by the protonophore FCCP. This fact indicates a neuroprotective effect, which increases when hypothermia changes from moderate to deep. The possible risks of using hypothermia in space medicine have been determined. Hypothermia is not able to reduce the extracellular level of L-[14C]glutamate and [3H]GABA, which increases under the conditions of exposure to carbon-containing planetary dust. Hypothermia can lead to a further decrease in the rate of accumulation of neurotransmitters in the presence of carbon-containing planetary dust and to contribute to the development of neurotoxicity, which is a possible risk of using hypothermia in space medicine. In this context, it is important to choose the optimal individual temperature regime for each astronaut.