Fastigial nucleus electrostimulation reduces the expression of repulsive guidance molecule, improves axonal growth following focal cerebral ischemia.

The role of repulsive guidance molecule A (RGMa) in cerebral ischemia remains unclear. In the study, we examined the expression of RGMa in ischemic brain tissues following focal cerebral ischemia/reperfusion (IR) in rats. An established middle cerebral artery suture occlusion model was employed. A dipolar electrode was placed into the cerebellum to stimulate the cerebellar fastigial nucleus for 1 h at 2 h after ischemia. Reverse transcription-polymerase chain reaction was used to measure the mRNA RGMa and its downstream mediator, Ras homolog A (RhoA). Immunohistochemistry was applied to detect RGMa and RhoA expressions and to evaluate axonal regeneration by optical density analysis of 200 kDa neurofilaments. We found that both mRNA and protein levels of RGMa and RhoA were increased in the ischemic cortex and hippocampus 48 h following cerebral IR and these elevated levels were maintained for 2 weeks. Electrostimulation of the fastigial nucleus reduced the expression of RGMa and RhoA at 24 h and 2 weeks following cerebral IR. In addition, axonal growth was enhanced in the fastigial nucleus electrostimulated group compared to non-stimulated ischemic animals (P < 0.05). RGMa/RhoA expression was negatively correlated with the growth of axons (P < 0.05). Therefore, we concluded that RGMa and RhoA could be another key molecule and might inhibit axonal regeneration during cerebral IR injury. Electrostimulation of the fastigial nucleus enhances axonal growth, possibly by reducing the expression of RGMa and RhoA after cerebral IR.