Traumatic brain injury is a highly prevalent medical condition for which no medications specific for the prophylaxis or treatment of the condition as a whole exist. The spectrum of symptoms includes coma, headache, seizures, cognitive impairment, depression, and anxiety. Although it has been known for years that the inhibitory neurotransmitter γ-amino-butyric acid (GABA) is involved in TBI, no novel therapeutics based upon this mechanism have been introduced into clinical practice. We review the neuroanatomical, neurophysiological, neurochemical, and neuropharmacological relationships of GABA neurotransmission to TBI with a view toward new potential GABA-based medicines. The long-standing idea that excitatory and inhibitory (GABA and others) balances are disrupted by TBI is supported by the experimental data but has failed to invent novel methods of restoring this balance. The slow progress in advancing new treatments is due to the complexity of the disorder that encompasses multiple dynamically interacting biological processes including hemodynamic and metabolic systems, neurodegeneration and neurogenesis, major disruptions in neural networks and axons, frank brain lesions, and a multitude of symptoms that have differential neuronal and neurohormonal regulatory mechanisms. Although the current and ongoing clinical studies include GABAergic drugs, no novel GABA compounds are being explored. It is suggested that filling the gap in understanding the roles played by specific GABA receptor configurations within specific neuronal circuits could help define new therapeutic approaches. Further research into the temporal and spatial delivery of GABA modulators should also be useful. Along with GABA modulation, research into the sequencing of GABA and non-GABA treatments will be needed.

中文翻译：

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创伤性脑损伤与γ-氨基丁酸（GABA）的机制和治疗关系

创伤性脑损伤是一种非常普遍的疾病，目前还没有专门用于预防或治疗该疾病的药物。一系列症状包括昏迷、头痛、癫痫、认知障碍、抑郁和焦虑。尽管多年来人们已经知道抑制性神经递质γ-氨基丁酸（GABA）与TBI有关，但尚未将基于该机制的新疗法引入临床实践。我们回顾了 GABA 神经传递与 TBI 的神经解剖学、神经生理学、神经化学和神经药理学关系，以期开发新的潜在基于 GABA 的药物。长期以来，TBI 破坏了兴奋性和抑制性（GABA 等）平衡的观点得到了实验数据的支持，但未能发明恢复这种平衡的新方法。新疗法进展缓慢是由于该疾病的复杂性，涉及多种动态相互作用的生物过程，包括血流动力学和代谢系统、神经变性和神经发生、神经网络和轴突的重大破坏、明显的脑损伤以及多种症状。具有不同的神经元和神经激素调节机制。尽管当前和正在进行的临床研究包括 GABA 能药物，但尚未探索新的 GABA 化合物。有人建议，填补了解特定神经元回路中特定 GABA 受体配置所发挥的作用的空白可能有助于定义新的治疗方法。对 GABA 调节剂的时间和空间传递的进一步研究也应该是有用的。除了 GABA 调节之外，还需要对 GABA 和非 GABA 治疗的测序进行研究。