Induction of astrocytic cytoplasmic phospholipase A2 and neuronal death after intracerebroventricular carrageenan injection, and neuroprotective effects of quinacrine

Abstract

Glial reaction is often associated with nervous tissue injury, but thus far, few studies have examined whether it can be a cause of neuronal injury. We now study the effect of intracerebroventricular injection of a carrageenan on cytoplasmic phospholipase A2 (cPLA2) expression and neuronal injury in the hippocampus. The enzyme cPLA2 hydrolyzes neural membrane glycerophospholipids and generates precursors for proinflammatory mediators. An induction of cPLA2 in astrocytes and death of neurons in the hippocampus were observed following glial reaction induced by intracerebroventricular injections of carrageenan. cPLA2 levels and neuronal death were modulated by daily intraperitoneal injections of quinacrine, an inhibitor of phospholipase A2 that can cross the blood brain barrier. These observations support a role for astrocytic cPLA 2 in mediating neuronal death. © 2003 Elsevier Science (USA). All rights reserved.