PMID: 8594208Oct 1, 1995Paper

Mediators of injury in neurotrauma: intracellular signal transduction and gene expression

Journal of Neurotrauma
N G BazanG Allan

Abstract

Membrane lipid-derived second messengers are generated by phospholipase A2 (PLA2) during synaptic activity. Overstimulation of this enzyme during neurotrauma results in the accumulation of bioactive metabolites such as arachidonic acid, oxygenated derivatives of arachidonic acid, and platelet-activating factor (PAF). Several of these bioactive lipids participate in cell damage, cell death, or repair-regenerative neural plasticity. Neurotransmitters may activate PLA2 directly when linked to receptors coupled to G proteins and/or indirectly as calcium influx or mobilization from intracellular stores is stimulated. The release of arachidonic acid and its subsequent metabolism to prostaglandins are early responses linked to neuronal signal transduction. Free arachidonic acid may interact with membrane proteins, i.e., receptors, ion channels, and enzymes, modifying their activity. It can also be acted upon by prostaglandin synthase isoenzymes (the constitutive prostaglandin synthase PGS-1 or the inducible PGS-2) and by lipoxygenases, with the resulting formation of different prostaglandins and leukotrienes. Glutamatergic synaptic activity and activation of postsynaptic NMDA receptors are examples of neuronal activity, linked to memo...Continue Reading

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