Glutamate and Cytokine-Mediated Alterations of Phospholipids in Head Injury and Spinal Cord Trauma

Abstract

Glutamate and cytokines play a major role in neurodegeneration and demyelination that occur following head injury and spinal cord trauma. Glutamate and cytokines produce their effect by stimulating glutamate and cytokine receptors and enhancing neural membrane phospholipid degradation through caspase-mediated activation of phospholipase A2. The stimulation of phospholipase A2 not only results in alteration in neural membrane composition and changes in neural membrane permeability and fluidity but also generates proinflammatory mediators, eicosanoids, and platelet activating factor, and oxidative stress mediators, isoprostanes, and 4-hydroxynonenal (4-HNE). The generation of these mediators along with the decrease in ATP and glutathione content, and generation of reactive oxygen species may contribute to neural cell death in head and spinal cord injury. Involvement of phospholipase A2 (PLA2) in neural cell injury suggests that phospholipase A2 inhibitors can limit neurodegeneration in head injury and spinal cord trauma and may therefore be used as potential drugs for the treatment of head and spinal cord injuries in animal models.