Neural Responses to Injury: Prevention, Protection and Research (Neuroscience Center of Excellence).
Abstract
As a consequence of traumatic brain injury (TBI), ischemia, and seizures, neurotransmitters are released and, in turn, generate an overproduction of second messengers. A key player in excitotoxic neuronal damage is the excitatory amino acid, glutumate (Olney, 1986; Rothman and Olney, 1986; Choi, 1988), which is released and accumulates in brain after TBI (Faden et al., 1989; Katayama et al., 1990; Nilsson et al., 1990) and ischemia (Benveniste et a'., 1984; Meidrum, 1990; Mitani et al., 1990; Christensen et al., 1991). Olutamate triggers increased permeation of calcium mediated by NMDA receptors and activation of many calcium dependent signaling pathways. Calcium-mediated activation of PLA2 and release of arachidonic acid (AA) are among the membrane lipid-derived signaling systems activated at the onset of these various forms of neurotrauma, which involve the over-release of neurotransmitters, the stimulation of post-synaptic receptors, and the subsequent accumulation of abnormally high concentrations of second messengers (Bazan et al., 1993; 1995). In our laboratory as well as in others, research has focused on the generation of injury mediators linked to the activation of calcium-dependent PLA2, the release of phospholipid derived bioactive lipid molecules, including free AA and platelet-activating factor (PAF), and the signaling pathways activated as a consequence (Bazan et al., 1991; 1994; 1995; Bonventre, 1996; Farooqui et al.,1997). PAF, in turn, promotes the expression of early genes (c-fos, c-jun, Zif 268) and others acting as early genes, such as the inducible cyclooxygenase COX-2 (Marcheselli and Bazan, 1994; 1996). The activation of COX-2 (PGHS-2) leads to a delayed accumulation of prostaglandins that, either per se or through the free radicals generated during their synthesis, activate a cascade of events leading to DNA degradation and cell death through apoptosis (Bazan, 1997).
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA369193
Entities
People
- Nicolas G Bazan
Organizations
- Louisiana State University