THE MOLECULAR AND CELLULAR SEQUELAE OF EXPERIMENTAL TRAUMATIC BRAIN INJURY - PATHOGENETIC MECHANISMS

The mechanisms underlying secondary or delayed cell death following tr aumatic brain injury (TBI) are poorly understood. Recent evidence from experimental models of TBI suggest that diffuse and widespread neuron al damage and loss is progressive and prolonged for months to years af ter the initial insult in selectively vulnerable regions of the cortex , hippocampus, thalamus, striatum, and subcortical nuclei. The develop ment of new neuropathological and molecular techniques has generated n ew insights into the cellular and molecular sequelae of brain trauma, This paper will review the literature suggesting that alterations in i ntracellular calcium with resulting changes in gene expression, activa tion of reactive oxygen species (ROS), activation of intracellular pro teases (calpains), expression of neurotrophic factors, and activation of cell death genes (apoptosis) mag play a role in mediating delayed c ell death after trauma. Recent data suggesting that TBI should be cons idered as both an inflammatory and/or a neurodegenerative disease is a lso presented. Further research concerning the complex molecular and n europathological cascades following brain trauma should be conducted, as novel therapeutic strategies continue to be developed.