Glutamate and post-traumatic cerebral excitoxicity as possible therapeutic targets – A literature review

Abstract

Cerebral edema and excitoxicity are well known phenomena and are reported in multiple pathological contexts. Despite that, regarding traumatic brain injury, significant events in incidence and potential clinical consequences, little is known about the actual promoting and modulating processes of cerebral damage, namely in relation to glutamate, the main excitatory endogenous neurotransmitter of the central nervous system. Based on current concepts on neuropathology and cerebral regulation, a thorough review is made on the glutamatergic regulation system, its role and mechanisms of action in a secondary response to TBI, namely in cortex and hippocampus, sensible areas to acute and delayed damage. Current and past clinical trials are also mentioned as attempts to modulate these events, with no clinical significance so far. A better knowledge of the glutamatergic deregulation and related excitoxicity should play a key role in the understanding of TBI and provide a basis for possible therapeutic targets in a close future.