Targeting neuroinflammation to treat cerebral ischemia - The role of TIGAR/NADPH axis

Abstract

Cerebral ischemia is a disease of ischemic necrosis of brain tissue caused by intracranial artery stenosis or occlusion and cerebral artery embolization. Neuroinflammation plays an important role in the pathophysiology of cerebral ischemia. Microglia, astrocytes, leukocytes and other cells that release a variety of inflammatory factors involved in neuroinflammation may play a damaging or protective role during the process of cerebral ischemia. TP53-induced glycolysis and apoptotic regulators (TIGAR) may facilitate the production of nicotinamide adenine dinucleotide phosphoric acid (NADPH) via the pentose phosphate pathway (PPP) to inhibit oxidative stress and neuroinflammation. TIGAR can also directly inhibit NF-κB to inhibit neuroinflammation. TIGAR thus protect against cerebral ischemic injury. Exogenous NADPH can inhibit neuroinflammation by inhibiting oxidative stress and regulating a variety of signals. However, since NADPH oxidase (NOX) may use NADPH as a substrate to generate reactive oxygen species (ROS) to mediate neuroinflammation, the combination of NADPH and NOX inhibitors may produce more powerful anti-neuroinflammatory effects. Here, we review the cells and regulatory signals involved in neuroinflammation during cerebral ischemia, and discuss the possible mechanisms of targeting neuroinflammation in the treatment of cerebral ischemia with TIGAR/NADPH axis, so as to provide new ideas for the prevention and treatment of cerebral ischemia.