Subarachnoid hemorrhage (SAH)—bleeding from a ruptured aneurysm—leads to delayed cerebral vasospasm (blood vessel constriction) and stroke. SAH morbidity and mortality are high, and therapeutic options are limited.
Joyce Cheung-Flynn, Ph.D., and colleagues proposed that SAH downregulates the nitric oxide-protein kinase G (NO-PKG) signaling pathway that normally relaxes cerebral blood vessels.
Using a rat model, they confirmed reduced levels of NO-PKG pathway molecules, including the protein VASP, which modulates contractile machinery to cause vasorelaxation. They designed a family of cell permeant peptide mimics of activated VASP and demonstrated that the peptides caused vasorelaxation of vascular tissues ex vivo.
The findings, reported in the European Journal of Pharmacology, suggest that reduced NO-PKG signaling is an underlying mechanism of pathological vasoconstriction after SAH. Treatment with activated VASP peptides could be explored as a therapeutic strategy to reduce neurological deficits caused by SAH-induced vasospasm, the authors suggest.