HCRT and ischemia: OX1 and OX2 share structural homology but mediate distinct physiological domains: OX1 drives rapid excitatory, arousal-promoting and immune-modulating responses, and is responsible for much of orexin’s cytoprotective and anti-apoptotic signaling after ischemia or trauma, whereas OX2 stabilizes wakefulness and autonomic tone [7,169].