Mitochondrial Dysfunction and Cerebral Energy Failure in Traumatic Brain Injury

Traumatic brain injury (TBI) encompasses a broad spectrum of neurological insults ranging from mild concussions to repeated head traumas, all of which induce complex metabolic disturbances in the brain. Mitochondria, as the cellular powerhouses, play a critical role in maintaining cerebral energy homeostasis by orchestrating oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and the electron transport chain (ETC). Following TBI, metabolic disruptions often manifest as glucose dysmetabolism, hyperglycolysis, and mitochondrial malfunctioning, leading to energy deficits that hinder neuronal recovery and neuroplasticity. Recent studies using advanced neuroimaging, metabolomics, and cellular analyses have revealed that impaired mitochondrial quality control, reduced pyruvate dehydrogenase activity, and altered lactate transporter function collectively drive energy failure and contribute to secondary injury cascades such as oxidative stress and neuroinflammation. Despite extensive experimental evidence, the precise temporal and molecular mechanisms linking mitochondrial dysfunction to clinical outcomes remain poorly understood, especially in recurrent injuries and chronic traumatic encephalopathy.

This Research Topic aims to elucidate the cellular and molecular underpinnings of mitochondrial dysfunction and energy failure in TBI to improve diagnosis, monitoring, and therapy. The main objectives are to identify potential mitochondrial biomarkers and mechanistic signatures of brain energy using multiomics approaches, to explore how mitochondrial dynamics and quality control pathways influence neuronal survival, and to establish the translational bridge between laboratory findings and clinical monitoring. Researchers are encouraged to address key questions such as how disturbances across the ETC, TCA cycle, and oxidative phosphorylation contribute to cerebral energy dysregulation, and how modulating these pathways could restore bioenergetic balance and cognitive function post-injury.

To gather further insights into mitochondrial-driven metabolic alterations in TBI, the Research Topic welcomes contributions that integrate molecular biology, neuroimaging, and clinical research. Submissions should define how mitochondrial dysfunction shapes the pathophysiology of TBI and inform therapeutic interventions. We welcome articles addressing, but not limited to, the following themes:

• Mechanisms of glucose dysmetabolism and energy failure following traumatic brain injury and concussion
• Roles of pyruvate dehydrogenase, lactate transporters, and the mitochondrial TCA cycle in energy metabolism
• Interactions among the electron transport chain, oxidative phosphorylation, and mitochondrial quality control
• Multiomics approaches for identifying mitochondrial biomarkers and monitoring energy status in clinical settings
• Therapeutic strategies to restore mitochondrial function and mitigate cerebral energy crisis after repeated head injuries
• Translational and imaging biomarkers linking mitochondrial malfunction with neurological and cognitive outcomes