While consistent with established mechanisms of the neuroprotective effects of neuronal CBS-derived H2S against ischemic brain injury [8] and exogenous H2S-mediated ROCK2 inhibition [27,50], our study innovatively identifies endothelial-derived H2S as the critical paracrine mediator regulating neuronal RhoA-ROCK2 signaling in a clinically relevant co-culture model. Here, CBS is linked to brain injury.