Figure 2.

Schematic drawing shows possible role of cPLA₂ in SCI.

SCI induces cPLA₂ expression and activation by several toxic factors that are generated in the injured cord including inflammatory cytokines, free radicals, and excitatory amino acids.

Over-activation of cPLA₂ induces cell death and tissue injury though several mechanisms.

First, cPLA₂ induces membrane damage through hydrolysis of neural membrane phospholipids, resulting in alternation of membrane function such as fluidity and permeability, behavior of transporters and receptors, and calcium overload, and, eventually, leading to functional failure of excitable membranes.

Second, cPLA₂ hydrolyzes membrane phospholipids to produce arachdonic acid (AA), then AA can give rise to pro-inflammatory mediators, for example eicosanoids, such as prostaglandins, thromboxanes, and leukotrienes.

Third, cPLA₂-induced AA and NADPH oxidase lead to ROS production. ANXA1, ATK and EGb761 reduce neuronal death and tissue damage though inhibition of cPLA₂.

cPLA_2: Cytosolic phospholipase A₂; AA: arachdonic acid; SCI: spinal cord injury; AA: arachdonic acid ANXA1: annexin A1; ATK: arachidonyl trifluromethyl ketone; EGb761: Ginkgo biloba extract; ROS: Reactive oxygen species; NADPH: nicotinamide adenine dinucleotide phosphate.