Since the absence of hypotension and dependence on reperfusion suggested that apo-sGC activators were acting via a previously unrecognized direct neuroprotective effect in agreement with the diseasome guided primary neuronal disease association, we investigated their direct effects on hypoxia-induced neuronal apoptosis, a well-established mechanism of tissue damage in ischemic stroke.34 Indeed, 24 h after stroke onset immunolabeling of TUNEL and NeuN revealed widespread apoptosis in the vehicle treated mice. Here, SGCB is linked to stroke disorder.