H2S-RhoA/ROCK Pathway and Glial Cells in Axonal Remyelination After Ischemic Stroke

Ischemic stroke is one of the main reasons of disability and death. Stroke-induced functional deficits are mainly due to the secondary degeneration of the white matter characterized by axonal demyelination and injury of axon-glial integrity. Enhancement of the axonal regeneration and remyelination could promote the neural functional recovery. However, cerebral ischemia-induced activation of RhoA/Rho kinase (ROCK) pathway plays a crucial and harmful role in the process of axonal recovery and regeneration. Inhibition of this pathway could promote the axonal regeneration and remyelination. In addition, hydrogen sulfide (H2S) has the significant neuroprotective role during the recovery of ischemic stroke via inhibiting the inflammatory response and oxidative stress, regulating astrocyte function, promoting the differentiation of endogenous oligodendrocyte precursor cells (OPCs) to mature oligodendrocyte. Among all of these effects, promoting the formation of mature oligodendrocyte is a crucial part of axonal regeneration and remyelination. Furthermore, numerous studies have uncovered the crosstalk between astrocytes and oligodendrocyte, microglial cells and oligodendrocyte in the axonal remyelination following ischemic stroke. The purpose of this review was to discuss the relationship among H2S, RhoA/ROCK pathway, astrocytes, and microglial cells in the axonal remyelination following ischemic stroke to reveal new strategies for preventing and treating this devastating disease.

Automated summary

Ischemic stroke is a major cause of disability and death, and enhancing axonal regeneration and remyelination can promote neural functional recovery. However, the activation of the RhoA/ROCK pathway plays a harmful role in axonal recovery and regeneration. Inhibition of this pathway can promote axonal regeneration and remyelination. Additionally, hydrogen sulfide (H2S) has a significant neuroprotective role in the recovery from ischemic stroke. This review discusses the relationship among H2S, the RhoA/ROCK pathway, astrocytes, and microglial cells in axonal remyelination following ischemic stroke, aiming to reveal new strategies for prevention and treatment of this devastating disease.