The roles of ROCK2/CBS-H₂S pathway in the cerebral ischemia/reperfusion injury

The purpose of present study was to demonstrate the effects and relationship of ROCK2 knockdown and cystathionine β-synthase (CBS)/H₂S in the neuronal injury and astrocytic function following cerebral ischemia/reperfusion (I/R). Wild type and ROCK2 knockdown mice were used to establish cerebral I/R model, and CBS knockdown astrocytes were used to establish the model of oxygen glucose deprivation/re‑oxygenation (OGD/R). We revealed that ROCK2 knockdown protects against cerebral I/R injury, as evidenced by reduced deficiency of exploratory behavior and decreased impairment of spatial memory, and suggested by reduced neuronal injury. Besides, ROCK2 knockdown improves the CBS expression and promotes H₂S release. Importantly, ROCK2 knockdown inhibits the proliferation of neurotoxic astrocytes and promotes the transformation of neuroprotective astrocytes. Furthermore, we found in the OGD/R model of astrocytes that down-regulation of CBS expression promotes the expressions of ROCK1 and ROCK2 and improves the astrocytic injury, which can be inhibited by H₂S supplement. Additionally, down-regulation of CBS expression improves the proliferation of neurotoxic astrocytes. While supplement with H₂S can promote the transformation of neuroprotective astrocytes. In conclusion, inhibition of ROCK2 can reduce the cerebral I/R injury via retaining neuroprotective function of astrocytes via promoting CBS/H₂S release, which in turn further inhibits the ROCKs expression.