TNF and ischemia: TNF-α-induced impairment of cerebrovascular function that associates to CBF deficits and secondary ischemia during SAH (Vecchione et al., 2009; Yagi et al., 2015) are thought to stem from altered S1P signaling as TNF-α alters S1P degradation, which leaves more S1P available for pro-constrictive S1PR2 signaling in mural cells (Figure 1).