Differential effects of calcium-dependent and calcium-independent phospholipase A2 inhibitors on kainate-induced neuronal injury in rat hippocampal slices

Brain tissue contains multiple forms of intracellular phospholipase A2 (PLA2) activity that differ from each other in many ways including their response to specific inhibitors. The systemic administration of kainic acid to rats produces a marked increase in cPLA2 activity in neurons and astrocytes. This is associated with increased lipid peroxidation as evidenced by accumulation of 4-hydroxynonenal (4-HNE) modified proteins. The present study describes the effect of specific inhibitors of Ca2+-dependent or Ca2+-independent PLA2 on kainite-induced excitotoxic injury in rat hippocampal slices. Specific inhibitors of Ca2+-dependent PLA2 prevented the decrease of a neuronal marker, GluR1, and increase in cPLA2 and 4-HNE immunoreactivities in slices treated with kainate. This shows that cPLA2 plays an important role in kainite-induced neurotoxicity and that cPLA2 inhibitors can be used to protect hippocampal slices from damage induced by kainate.