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

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 A(2) (cPLA(2)) expression and neuronal injury in the hippocampus. The enzyme cPLA(2) hydrolyzes neural membrane glycerophospholipids and generates precursors for proinflammatory mediators. An induction of cPLA(2) in astrocytes and death of neurons in the hippocampus were observed following glial reaction induced by intracerebroventricular injections of carrageenan. cPLA(2) levels and neuronal death were modulated by daily intraperitoneal injections of quinacrine, an inhibitor of phospholipase A(2) that can cross the blood brain barrier. These observations support a role for astrocytic cPLA(2) in mediating neuronal death.