title: The mitochondrial permeability transition pore provides a key to the diagnosis and treatment of traumatic brain injury.
abstract: The pathological consequences of traumatic head injury result largely from the opening of the mitochondrial permeability transition pore (mPTP). The mPTP opens due to a decrease in brain phosphorylation energy resulting in a further decrease in brain ATP production and a measurable increase in brain heat generation and temperature. The increase in brain temperature can be measured transcranially by near infrared spectroscopy which can be used to diagnose traumatic brain injury (TBI) and to monitor treatment. Effective therapy of TBI can be achieved by closure of the mPTP by administration of cyclosporine A or by oral administration of ketone body esters. While ketosis has previously been known to prevent damage from TBI, the availability of oral ketone esters presents the first practical modality of achieving therapeutic levels of ketone bodies.
authors.affiliation: Laboratory of Metabolic Control, NIAAA, NIH, Rockville, MD 20852, USA. rveech@mail.nih.gov
authors.forename: Richard L
authors.initials: RL
authors.lastname: Veech
authors.forename: C Robert
authors.initials: CR
authors.lastname: Valeri
authors.forename: Theodore B
authors.initials: TB
authors.lastname: VanItallie
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016572:Cyclosporine / Q000627:therapeutic use; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D058990:Molecular Targeted Therapy; D013055:Spectrophotometry, Infrared
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016572:Cyclosporine