Roles of Platelet-Activating Factor in Brain

Platelet-activating factor (PAF) is a bioactive phospholipid that activates a number of cells including neural cells (neurons, astrocytes, oligodendrocytes, and microglia), platelets, leukocytes, monocytes, macrophages, endothelial cells, and smooth muscle cells (Aihara et al., 2000) (Montrucchio et al., 2000). A variety of stimuli, including those producing inflammation, promote the synthesis and release of PAF from neural and nonneural cells. As PAF interacts with many types of nonneural cells, it mediates processes as diverse as wound healing, physiological inflammation, angiogenesis, apoptosis, and reproduction (Montrucchio et al., 2000). Physiological concentrations (1–100 nM) of PAF promote differentiation in developing neurons and increase the strength of synaptic transmission in the mature brain. Higher concentrations of PAF (μM) that occur in pathological conditions such as head and spinal cord trauma and ischemia trigger neuronal cell death (Bazan et al., 1997; Kornecki et al., 1996). In brain tissue, PAF may be associated with neural cell migration, gene expression, calcium mobilization, noniception, and long-term potentiation (Fig. 9.1). PAF interacts with neural and nonneural cells by binding to specific receptors called as PAF receptors (PAF-Rs). These receptors have been cloned and characterized from nonneural tissues (Honda et al., 1991). Like G protein-coupled receptors, PAF-Rs possess seven transmembrane helices and signals through several G proteins such as Gαo, Gαi, Gβγ, and Gαq. PAF-Rs are associated with multiple intracellular signaling pathways (Honda et al., 1991; Clark et al., 2000).

In the cardiovascular system, PAF plays a role in embryogenesis because it regulates endothelial cell migration and angiogenesis, and may modulate cardiac function because it exhibits mechanical and electrophysiological actions on cardiomyocytes (Montrucchio et al., 2000). Moreover, PAF may contribute to the modulation of blood pressure mainly by affecting the renal vascular circulation. In pathological conditions, PAF has been involved in the hypotension and cardiac dysfunctions occurring in various cardiovascular stress situations such as cardiac anaphylaxis and hemorrhagic, traumatic, and septic shock syndromes (Montrucchio et al., 2000).


Tactile Allodynia Collective Evidence Granule Cell Migration Nonneural Cell Postsynaptic NMDA Receptor 
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