Metabolic and endocrine dysfunctions in traumatic brain injury: Implications for cognitive recovery and therapeutic...

Traumatic brain injury (TBI) triggers a chain reaction of intricate metabolic abnormalities, sometimes leading to ongoing cognitive deficits. These abnormalities comprise dysregulation in trace element homeostasis, disrupted neurotransmitter modulation, increased lipid peroxidation, compromised glucose metabolism, and organ-specific metabolic changes. Most recent studies suggest that metabolic abnormalities are the root cause of cognitive decline in post-traumatic stress disorder. Restoring metabolic balance through therapeutic modalities, such as antioxidant therapy to combat lipid peroxidation, glucose modulators to normalise cerebral energy metabolism, and trace element supplementation, shows promise. Furthermore, increasingly understood as important determinant of long-term neurocognitive outcomes are endocrine dysfunctions, especially post-traumatic hypopituitarism and growth hormone deficiency (GHD). Growth hormone replacement therapy has been shown to improve cognitive function and overall recovery. Biomarkers such as insulin-like growth factor-1 (IGF-1), neuroinflammatory cytokines (IL-6 and TNF-α), and oxidative stress markers (like malondialdehyde) can facilitate early diagnosis, which may allow for targeted and timely intervention. This review is metabolism-oriented, biomarker-guided therapeutic approaches to improve neurocognitive recovery and patient quality of life, highlighting the critical role that metabolic and endocrine abnormalities play in post-TBI cognitive impairment.