TNF and brain ischemia: Our results tally well with previous studies showing that induced MC4R activation on microglia and astrocytes elicits anti-inflammatory effects by stimulating the cholinergic pathway and the adenosine monophosphate-activated protein kinase (AMPK)/c-Jun N-terminal kinase (JNK)/p38 MAPK (41, 42); these studies demonstrated a prominent role of MCRs in reducing release of cytokines/mediators, such as TNFα, IL1ß, IL6 and reactive oxygen species, and pro apoptotic marker Bax, in experimental cerebral ischemia/reperfusion, traumatic brain injury and LPS-induced neuroinflammation (22, 42, 43).