title: Evidence to support mitochondrial neuroprotection, in severe traumatic brain injury.
abstract: Traumatic brain injury (TBI) is still the leading cause of disability in young adults worldwide. The major mechanisms - diffuse axonal injury, cerebral contusion, ischemic neurological damage, and intracranial hematomas have all been shown to be associated with mitochondrial dysfunction in some form. Mitochondrial dysfunction in TBI patients is an active area of research, and attempts to manipulate neuronal/astrocytic metabolism to improve outcomes have been met with limited translational success. Previously, several preclinical and clinical studies on TBI induced mitochondrial dysfunction have focused on opening of the mitochondrial permeability transition pore (PTP), consequent neurodegeneration and attempts to mitigate this degeneration with cyclosporine A (CsA) or analogous drugs, and have been unsuccessful. Recent insights into normal mitochondrial dynamics and into diseases such as inherited mitochondrial neuropathies, sepsis and organ failure could provide novel opportunities to develop mitochondria-based neuroprotective treatments that could improve severe TBI outcomes. This review summarizes those aspects of mitochondrial dysfunction underlying TBI pathology with special attention to models of penetrating traumatic brain injury, an epidemic in modern American society.
authors.affiliation: Department of Neurosurgery, Miller School of Medicine, University of Miami, Lois Pope LIFE Center, Room 3-20, 1095 NW 14th Terrace, Miami, FL, 33136, USA.
authors.forename: Shyam
authors.initials: S
authors.lastname: Gajavelli
authors.forename: Vishal K
authors.initials: VK
authors.lastname: Sinha
authors.forename: Anna T
authors.initials: AT
authors.lastname: Mazzeo
authors.forename: Markus S
authors.initials: MS
authors.lastname: Spurlock
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Lee
authors.forename: Aminul I
authors.initials: AI
authors.lastname: Ahmed
authors.forename: Shoji
authors.initials: S
authors.lastname: Yokobori
authors.forename: Ross M
authors.initials: RM
authors.lastname: Bullock
mesh_terms: D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D063154:Mitochondrial Dynamics; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D019636:Neurodegenerative Diseases / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore