Traumatic brain injury (TBI) is increasingly viewed as a metabolic disorder rather than purely structural damage. This narrative review synthesises studies of mitochondrial physiology, brain thermodynamics and metabolic interventions to show that opening of the mitochondrial permeability transition pore (mPTP) underlies the energetic collapse after TBI. Opening the pore dissipates the mitochondrial membrane potential, decreases ATP production and leads to heat generation and ionic imbalance, which can be detected using near‑infrared spectroscopy.

Traumatic brain injury (TBI) is increasingly viewed as a metabolic disorder rather than purely structural damage. This narrative review synthesises studies of mitochondrial physiology, brain thermodynamics and metabolic interventions to show that opening of the mitochondrial permeability transition pore (mPTP) underlies the energetic collapse after TBI. Opening the pore dissipates the mitochondrial membrane potential, decreases ATP production and leads to heat generation and ionic imbalance, which can be detected using near‑infrared spectroscopy.

The authors compare cyclosporine A, which binds cyclophilin and closes the mPTP but has nephro‑ and hepatotoxicity, with ketogenic strategies that increase circulating ketone bodies. Fasting, ketogenic diets and a ketone monoester (D‑β‑hydroxybutyrate/R‑1,3‑butanediol) rapidly raise blood β‑hydroxybutyrate to 5–7 mM within an hour, increasing phosphorylation potential and closing the mPTP. Elevating ketone bodies reduces brain temperature, restores ionic balance and offers a practical, non‑toxic approach to TBI treatment and diagnosis. Controlled clinical studies are needed to validate these interventions and optimise dosing.The authors compare cyclosporine A, which binds cyclophilin and closes the mPTP but has nephro‑ and hepatotoxicity, with ketogenic strategies that increase circulating ketone bodies. Fasting, ketogenic diets and a ketone monoester (D‑β‑hydroxybutyrate/R‑1,3‑butanediol) rapidly raise blood β‑hydroxybutyrate to 5–7 mM within an hour, increasing phosphorylation potential and closing the mPTP. Elevating ketone bodies reduces brain temperature, restores ionic balance and offers a practical, non‑toxic approach to TBI treatment and diagnosis. Controlled clinical interventions and optimise dosing.Dark, minimalist science‑tech diagram showing the mitochondrial permeability transition pore (mPTP) as the central glowing node. Connections radiate to outcomes like “Neuroprotection”, “Brain Temperature” and “ATP Production”, highlighting how closing the pore restores energy balance. Background features subtle gridlines and concentric rings to evoke scientific precision and neuroimaging. Use a dark charcoal background with teal and orange accents. Ultra‑modern, clinical UI aesthetic—no people or products—emphasising the concept of mPTP modulation.