Chapter 52 – Lipid Mediators

Phospholipids of nervous system cellular membranes are reservoirs for bioactive lipid mediators. Cerebral ischemia disrupts tightly regulated events controlling the production and accumulation of lipid messengers, such as free docosahexaenoic (DHA) and arachidonic acids, diacylglycerol, and platelet-activating factor (PAF). These messengers participate in intracellular and/or intercellular signaling pathways. Bioactive lipids have actions on neurotransmitter release, synaptic plasticity, and programs of neural cell gene expression that ultimately regulate cell survival. PAF transcriptional activation of COX-2 provides clues about novel neuronal cell death pathways. PAF accumulates during cerebral ischemia, and inhibition of this process plays a critical role in neuronal survival. DHA in phospholipids is also a reservoir for biologically active docosanoids. Neuroprotectin D1 is a prototypical docosanoid made on demand when uncompensated oxidative stress ensues and/or at the onset of homeostasis disruptions. In this chapter, the significance of selected lipid messengers on synaptic function, neuronal gene expression, and neuroprotection as they relate to cerebral ischemia is discussed.