Fig. 2

Possible pathways leading to vascular spasm. A Ca2+-related pathway: Blood products may activate G protein-coupled receptors and activate the RhoA/Rho-associated protein kinase signalling pathway, elevating myosin light chain kinase (MLCK) activity. The G protein-coupled receptor activates phospholipase C, leading to the hydrolysis of phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3, in turn, induces Ca2+ release from Ca2+ stores, while DAG activates PKC, reducing MLCP activity and increasing MLCK activity. Blood products activate receptor tyrosine kinases, which induce extracellular Ca2+ influx. B Oxygenated haemoglobin pathway: this pathway increases the production of reactive oxygen species (ROS) and endothelin-1 in astrocytes. ROS can cause degradation and inactivation of NO, reduce NO production, and induce phospholipase A2 metabolism, ultimately yielding PGF2a and TXA2 and promoting vasoconstriction. ROS-mediated lipid peroxides also have a vasoconstrictive effect on blood vessels. By inhibiting the NO/cGMP signalling pathway, this process transforms the phenotype of the surrounding cells into a contractile phenotype. Furthermore, it directly elevates endothelin-1 levels in endothelial cells and vascular smooth muscle cells (VSMCs), causing increased adhesion molecule expression, ultimately leading to leukocyte aggregation and ET-1 release. C Enhanced neuronal activity activates Ca2+ channels in VSMCs or surrounding cells, inducing vasoconstriction