Traumatic brain injury: developmental differences in glutamate receptor response and the impact on treatment.
Perinatal brain injury following trauma, hypoxia, and/or ischemia represents a substantial cause of pediatric disabilities including mental retardation. Such injuries lead to neuronal cell death through either necrosis or apoptosis. Numerous in vivo and in vitro studies implicate ionotropic (iGluRs) and metabotropic (mGluRs) glutamate receptors in the modulation of such cell death. Expression of glutamate receptors changes as a function of developmental age, with substantial implications for understanding mechanisms of post-injury cell death and its potential treatment. Recent findings suggest that the developing brain is more susceptible to apoptosis after injury and that such caspase mediated cell death may be exacerbated by treatment with N-methyl-D-aspartate receptor antagonists. Moreover, group I metabotropic glutamate receptors appear to have opposite effects on necrotic and apoptotic cell death. Understanding the relative roles of glutamate receptors in post-traumatic or post-ischemic cell death as a function of developmental age may lead to novel targeted approaches to the treatment of pediatric brain injury.
Lea
P M
PM
Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
Faden
A I
AI
D000367:Age Factors; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D009336:Necrosis; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012720:Severity of Illness Index
D015220:Calcium Channels; D020169:Caspases; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate