Chapter 20 Glutamate and its receptors in the pathophysiology of brain and spinal cord injuries

Abstract

Publisher Summary This chapter reviews the contribution of the excitatory neurotransmitter glutamate to central nervous system (CNS) damage following traumatic brain injury (TBI) and spinal cord injuries (SCI), and in particular the evidence for glutamate-induced neuronal damage in head-injured patients. Studies have focused on the prevention of secondary damage and the regeneration of damaged neuronal tissue TBI or SCI injury. Targets for the prevention of secondary damage are glutamatergic, cholinergic, and catecholaminergic neurotransmission systems; free radical production; lipid peroxidation; calcium channels; growth factors; inflammation processes; endogenous opioid receptors; enzymes; apoptotic cell death; repair mechanisms; and others. Traumatic brain or spinal cord injury results in neurological dysfunction and death, through both direct and indirect mechanisms. Glutamate seems to have a more important role in the pathogenesis of non-hemorrhagic/hemorrhagic focal contusions. Cerebral contusions are focal injuries, which result when localized mechanical forces damage blood vessels, neurons, neurophils, and astrocytes. The wide spectrum of beneficial effects shown by various pharmacological antagonists to glutamate, and its co-agonists in numerous TBI-relevant animal models, has been a powerful impetus to the pharmaceutical industry to evaluate glutamate antagonists in TBI clinical trials.