CALCA and brain ischemia: In conclusion, CGRP can induce vasodilation of local cerebral ischemia by directly activating the cAMP–PKA pathway in vascular smooth muscle cells and by indirectly activating the NO–cGMP pathway in an endothelial cell-dependent manner (Figure 1), thus rapidly increasing ischemic local blood flow together with reperfusion, cooperatively protecting the brain tissue of ischemic penumbra by ischemia and hypoxia-induced damage, and reducing infarct size.