Mitochondrial dysfunction contributes to cell death following traumatic brain injury in adult and immature animals.
Secondary injury following traumatic brain injury (TBI) is characterized by a variety of pathophysiologic cascades. Many of these cascades can have significant detrimental effects on cerebral mitochondria. These include exposure of neurons to excitotoxic levels of excitatory neurotransmitters with intracellular calcium influx, generation of reactive oxygen species, and production of peptides that participate in apoptotic cell death. Both experimental and clinical TBI studies have documented mitochondrial dysfunction, and animal studies suggest this dysfunction begins early and may persist for days following injury. Furthermore, interventions targeting mitochondrial mechanisms have shown neuroprotection after TBI. Continued evaluation and understanding of mitochondrial mechanisms contributing to neuronal cell death and survival after TBI is indicated. In addition, important underlying factors, such as brain maturation, that influence mitochondrial function should be studied. The ability to identify, target, and manipulate mitochondrial dysfunction may lead to the development of novel therapies for the treatment of adult and pediatric TBI.
Robertson
Courtney L
CL
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. croberts@peds.umaryland.edu
D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001930:Brain Injuries / Q000188:drug therapy / Q000196:embryology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000196:embryology / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage
D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents; D045304:Cytochromes c; D002118:Calcium