Neurological Manifestations Following Traumatic Brain Injury: Role of Behavioral, Neuroinflammation, Excitotoxicity, Nrf-2 and Nitric Oxide.

Lav Goyal, Shamsher Singh
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Abstract

Traumatic Brain Injury (TBI) is attributed to a forceful impact on the brain caused by sharp, penetrating bodies, like bullets and any sharp object. Some popular instances like falls, traffic accidents, physical assaults, and athletic injuries frequently cause TBI. TBI is the primary cause of both mortality and disability among young children and adults. Several individuals experience psychiatric problems, including cognitive dysfunction, depression, post-traumatic stress disorder, and anxiety, after primary injury. Behavioral changes post TBI include cognitive deficits and emotional instability (anxiety, depression, and post-traumatic stress disorder). These alterations are linked to neuroinflammatory processes. On the other hand, the direct impact mitigates inflammation insult by the release of pro-inflammatory cytokines, namely IL-1β, IL-6, and TNF-α, exacerbating neuronal injury and contributing to neurodegeneration. During the excitotoxic phase, activation of glutamate subunits like NMDA enhances the influx of Ca2+ and leads to mitochondrial metabolic impairment and calpain-mediated cytoskeletal disassembly. TBI pathological insult is also linked to transcriptional response suppression Nrf-2, which plays a critical role against TBI-induced oxidative stress. Activation of NRF-2 enhances the expression of anti-oxidant enzymes, providing neuroprotection. A possible explanation for the elevated levels of NO is that the stimulation of NMDA receptors by glutamate leads to the influx of calcium in the postsynaptic region, activating NOS's constitutive isoforms.

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创伤性脑损伤后的神经表现:行为、神经炎症、兴奋毒性、Nrf-2 和一氧化氮的作用。
创伤性脑损伤(TBI)是由于子弹或任何尖锐物体等锋利的、具有穿透力的物体对大脑造成的强烈撞击所致。一些常见的情况,如跌倒、交通事故、人身攻击和运动损伤,经常会导致创伤性脑损伤。创伤性脑损伤是造成幼儿和成年人死亡和残疾的主要原因。一些人在初次受伤后会出现精神问题,包括认知功能障碍、抑郁、创伤后应激障碍和焦虑。创伤性脑损伤后的行为变化包括认知障碍和情绪不稳定(焦虑、抑郁和创伤后应激障碍)。这些变化与神经炎症过程有关。另一方面,直接影响通过释放促炎细胞因子(即 IL-1β、IL-6 和 TNF-α)减轻炎症损伤,加剧神经元损伤并导致神经变性。在兴奋毒性阶段,谷氨酸亚单位(如 NMDA)的激活增强了 Ca2+ 的流入,导致线粒体代谢障碍和钙蛋白酶介导的细胞骨架解体。创伤性脑损伤的病理损伤还与转录反应抑制 Nrf-2 有关,Nrf-2 对创伤性脑损伤诱导的氧化应激起着关键作用。激活 NRF-2 可增强抗氧化酶的表达,从而提供神经保护。氮氧化物水平升高的一个可能解释是,谷氨酸刺激 NMDA 受体导致钙离子流入突触后区域,激活了 NOS 的组成异构体。
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