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The connection between central nervous system injury and central nervous system injury\u2013associated immunodepression syndrome is not fully clear. Gamma-aminobutyric acid, an important inhibitory neurotransmitter, helps excitation-inhibition balance in the nervous system, especially after spinal cord injuries. Impaired gamma-aminobutyric acid signaling causes an excitation-inhibition imbalance, which worsens neural plasticity, increases sympathetic overactivity, and may lead to central nervous system injury\u2013associated immunodepression syndrome. This review discusses the roles of gamma-aminobutyric acid in protecting central nervous system structure and function and how its dysfunction contributes to abnormal plasticity and heightened reflexes. We also explore new treatments aimed at restoring gamma-aminobutyric acid balance, such as modulating potassium-chloride cotransporter 2, enhancing activity-dependent recovery, targeting microglial responses, and dietary approaches. Maintaining healthy gamma-aminobutyric acid activity is essential for preventing immune issues following central nervous system injury. This review emphasizes the regulation of gamma-aminobutyric acid as a promising target for future treatments of central nervous system injury-associated immunodepression syndrome.<\/jats:p>","DOI":"10.4103\/nrr.nrr-d-25-00147","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T06:00:58Z","timestamp":1756965658000},"page":"3997-4011","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Restoration of gamma-aminobutyric acid homeostasis: A novel approach to alleviating central nervous system injury\u2013associated immunodepression syndrome"],"prefix":"10.4103","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7914-3624","authenticated-orcid":false,"given":"Ping","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Army Medical University, Chongqing, 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