Metabolism and inflammation: implications for traumatic brain injury therapeutics

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Killen, Monica J 
Giorgi-Coll, Susan 
Hutchinson, Peter JA 
Carpenter, Keri LH 

Introduction: Traumatic Brain Injury (TBI) is a leading cause of death and disability in young people, affecting 69 million people annually, worldwide. The initial trauma disrupts brain homeostasis resulting in metabolic dysfunction and an inflammatory cascade, which can then promote further neurodegenerative effects for months or years, as a ‘secondary’ injury. Effective targeting of the cerebral inflammatory system is challenging due to its complex, pleiotropic nature. Cell metabolism plays a key role in many diseases, and increased disturbance in the TBI metabolic state is associated with poorer patient outcomes. Investigating critical metabolic pathways, and their links to inflammation, can potentially identify supplements which alter the brain’s long-term response to TBI and improve recovery. Areas covered: The authors provide an overview of literature on metabolism and inflammation following TBI, and from relevant pre-clinical and clinical studies, propose therapeutic strategies. Expert commentary: There is still no specific active drug treatment for TBI. Changes in metabolic and inflammatory states have been reported after TBI and appear linked. Understanding more about abnormal cerebral metabolism following TBI, and its relationship with cerebral inflammation, will provide essential information for designing therapies, with implications for neurocritical care and for alleviating long-term disability and neurodegeneration in post-TBI patients.

Inflammation, lactate pyruvate ratio (LPR), metabolic dysfunction, metabolism, supplementation, traumatic brain injury (TBI), Anti-Inflammatory Agents, Brain, Brain Injuries, Traumatic, Humans, Inflammation, Young Adult
Journal Title
Expert Review of Neurotherapeutics
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Taylor & Francis
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (G0802251)
Royal College of Surgeons of England (2016/2017)
Academy of Medical Sciences (Unknown)
Medical Research Council (G1002277)
MJK - Cambridge Australia Oliphant Scholarship in partnership with the Cambridge Trust; SGC – National Institute for Health Research Biomedical Research Centre, Cambridge; PJH – National Institute for Health Research (NIHR) Research Professorship, Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship and the National Institute for Health Research Biomedical Research Centre, Cambridge; KLHC - KLHC – National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme). Our cerebral metabolism studies were funded by the Medical Research Council (Grant No. G1002277, ID98489). Our cytokine studies were supported by a joint Medical Research Council/Royal College of Surgeons of England Clinical Research Training Fellowship (G0802251) awarded to AH.