Differential effects of calcium-dependent and calcium-independent phospholipase A(2) inhibitors on kainate-induced neuronal injury in rat hippocampalslices

Brain tissue contains multiple forms of intracellular phospholipase A(2) (P LA(2)) activity that differ from each other in many ways including their re sponse to specific inhibitors. The systemic administration of kainic acid t o rats produces a marked increase in cPLA(2) activity in neurons and astroc ytes. This is associated with increased lipid peroxidation as evidenced by accumulation of 4-hydroxynonenal (4-HNE) modified proteins. The present stu dy describes the effect of specific inhibitors of Ca2+ -dependent or Ca2+ - independent PLA(2) on kainite-induced excitotoxic injury in rat hippocampal slices. Specific inhibitors of Ca2+ -dependent PLA(2) prevented the decrea se of a neuronal marker, GluR1, and increase in cPLA(2) and 4-HNE immunorea ctivities in slices treated with kainate. This shows that cPLA(2) plays an important role in kainite-induced neurotoxicity and that cPLA(2) inhibitors can be used to protect hippocampal slices from damage induced by kainate. (C) 2001 Elsevier Science Inc.