TNF and Stroke: Following the onset of stroke, cerebral blood flow in the infarct area becomes significantly reduced, which induces necrotic death of resident neurons.199 Necrosis is an unprogrammed cell death process caused mainly by decreased ATP in ischemia.31 Recent studies have reported necrosis to be a highly regulated process involving various signaling pathways.200 The major downstream signaling pathways controlled by TNF-α include receptor-interacting protein kinase (RIPK1 and RIPK3) and mixed lineage kinase domain-like pathways.201