Neuroinflammation aggravated by traumatic brain injury at high altitude is reversed by L-serine via NFAT1-mediated microglial polarization

作者：Jinchun Liu, Shunhua Peng, Lisha Ye, Yechao Sun, Zhao Qiong, Hua Wei, Qianqian Luo, Min He, Guohua Wang · 发表于：Frontiers in Cellular Neuroscience · 年份：2023 · DOI：10.3389/fncel.2023.1152392 · 被引用次数：20 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Neuroscience of respiration and sleep、Prenatal Substance Exposure Effects

Traumatic brain injury (TBI) is one of the main causes of disability and death, especially in plateau areas, where the degree of injury is often more serious than in plain areas. It is likely that high altitude (HA) aggravates neuroinflammation; however, prior studies are limited. This study was designed to evaluate the effects of HA on the degree of TBI and the neuroprotective effects and underlying mechanisms of L-serine against TBI at HA (HA-TBI). In in vivo experiments, wild-type mice and mice with Nfat1 ( Nfat1 −/− ) deficiency in the C57BL/6 background were kept in a hypobaric chamber for 3 days under simulated conditions of 4,000 m, 6,000 m and 8,000 m above sea level. After leaving the chamber, the standardized TBI model was established immediately. Mice were then intraperitoneally injected with L-serine (342 mg.kg −1 ) 2 h after TBI and then daily for 5 days. Behavioral tests and histological analysis were assessed at different time points post TBI induction. In vitro , we applied primary cultured microglia for hypoxia treatment (1% O 2 for 24 h). The major findings include the following: (1) with increasing altitude, the neurological function of TBI mice decreased, and the damage to cerebral gray matter and white matter became more significant, (2) L-serine significantly improved the sensorimotor function of mice, reversed the increase in brain lesion volume, and promoted the renovation of brain tissue after HA-TBI, (3) L-serine significantly decreased the activatio...