Traumatic brain injury: Developmental differences in glutamate receptor response and the impact on treatment

Perinatal brain injury following trauma, hypoxia, and/or ischemia represent s a substantial cause of pediatric disabilities including mental retardatio n. Such injuries lead to neuronal cell death through either necrosis or apo ptosis. Numerous in vivo and in vitro studies implicate ionotropic (iGluRs) and metabotropic (mGluRs) glutamate receptors in the modulation of such ce ll death. Expression of glutamate receptors changes as a function of develo pmental 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 an d that such caspase mediated cell death may be exacerbated by treatment wit h N-methyl-D-aspartate receptor antagonists. Moreover, group 1 metabotropic glutamate receptors appear to have opposite effects on necrotic and apopto tic cell death. Understanding the relative roles of glutamate receptors in post-traumatic or post-ischemic cell death as a function of developmental a ge may lead to novel targeted approaches to the treatment of pediatric brai n injury. (C) 2001 Wiley-Liss, Inc.