Blockage of cytosolic phospholipase A2 alpha by monoclonal antibody attenuates focal ischemic brain damage in mice

The purposes of the current study were to investigate the effects of a monoclonal antibody (mAb) on cytosolic phospholipase A2 alpha (cPLA2 alpha) in mice with cerebral ischemiareperfusion (IR) injury and to ascertain the potential mechanisms of those effects. This study evaluated whether the use of anti-cPLA2 alpha mAb could reduce stroke injury in a mouse model of cerebral IR injury. The expression/ activity of cPLA2 alpha and cPLA2 alpha derived proinflammatory lipid mediators such as prostaglandin E2 (PGE2), leukotriene B4 (LTB4), lysophosphatidylcholine (LPC), and free fatty acids (FFA) was assessed. This study also evaluated neurological deficits, motor function, pathological changes, apoptosis, and the area of infarction in the injured mice. Mice treated with anti-cPLA2 alpha mAb recovered neurological function and their condition improved, apoptosis in the brain decreased and infarct volume decreased, and expression of cPLA2 alpha, 5-LOX, COX-2, FFA, LPC, PGE2, and LTB4 was attenuated. Our findings indicate that cPLA2 alpha plays a key role in cerebral IR injury and that treatment with anti-cPLA2 alpha cmAb after cerebral IR injury helps to reduce levels of proinflammatory cytokines, alleviate tissue damage, and reduce levels of deleterious lipid mediators. Thus, anti-cPLA2 alpha mAb treatment has the potential to treat ischemic brain damage.