TNF-α is a critical proinflammatory cytokine released from M1 microglial cells following ischemia, which serves as an activator of receptor-mediated proapoptotic pathways within the neuron, and can further stimulate microglia via inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 [46]. The gene discussed is NOS2; the disease is ischemia.