Phospholipases A₂ in ischemic and toxic brain injury

Phospholipases A₂ (PLA₂s) regulate hydrolysis of fatty acids, including arachidonic acid, from the sn-2 position of phospholipid membranes. PLA₂ activity has been implicated in neurotoxicity and neurodegenerative processes secondary to ischemia and reperfusion and other oxidative stresses. The PLA₂s constitute a superfamily whose members have diverse functions and patterns of expression. A large number of PLA₂s have been identified within the central nervous systems of rodents and humans. We postulated that group IV large molecular weight, cytosolic phospholipase A₂ (cPLA₂) has a unique role in neurotoxicity associated with ischemic or toxin stress. We created mice deficient in cPLA₂ and tested this hypothesis in two injury models, ischemia/reperfusion and MPTP neurotoxicity. In each model cPLA₂ deficient mice are protected against neuronal injury when compared to their wild type littermate controls. These experiments support the hypothesis that cPLA₂ is an important mediator of ischemic and oxidative injuries in the brain.