Abstract: Injuries to the central nervous system can disrupt body functions and often cause excessive sympathetic activity, leading to immune suppression known as central nervous system injury–associated immunodepression syndrome. The connection between central nervous system injury and central nervous system injury–associated 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–associated 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. 

Key words: activity-dependent rehabilitation, central nervous system injury–associated immunodepression syndrome, dietary interventions, excitatory-inhibitory balance, gamma-aminobutyric acid, microglial modulation, nerve regeneration, potassium -chloride cotransporter 2, spinal cord injury, sympathetic hyperreflexia