The relationship among H₂S, neuroinflammation and MMP-9 in BBB injury following ischemic stroke

Blood-brain barrier (BBB) is located at the interface between the central nervous system (CNS) and the circulatory system, which maintains the microenvironmental homeostasis of the CNS. BBB damage is a result of CNS diseases, including ischemic stroke, and is a cause of CNS deterioration. Cerebral ischemia unleashes a profound inflammatory response to remove the damaged tissue in the CNS and prepare the brain for repair. However, the excessive neuroinflammation following stroke onset is associated with BBB breakdown, resulting in neuronal injury and worse neurological outcomes. Additionally, matrix metalloproteinases (MMPs) are likewise responsible for the BBB injury and participate in the pathological processes of neuroinflammation following ischemic stroke. Hydrogen sulfide (H₂S) is one of gaseous signaling and freely diffusing molecules. Low concentration of H₂S yields the neuroprotection against BBB damage following stroke. This review discussed the current knowledge about the detrimental roles of neuroinflammation and MMPs in BBB injury following ischemic stroke. Specifically, we provided an updated overview of H₂S in protecting against BBB injury following ischemic stroke via anti-neuroinflammation and inhibiting MMP-9.