Combination of constraint-induced movement therapy with fasudil amplifies neurogenesis after focal cerebral ischemia/reperfusion in rats

Abstract

Purpose

Spontaneous axonal plasticity and functional restoration after stroke may be limited by Nogo-A, a myelin-associated inhibitor, via activation of the Rho/Rho-associated protein kinase (ROCK) pathway. Constraint-induced movement therapy (CIMT) is a rehabilitation technique based on neuroplasticity and neural recombination. We recently reported that CIMT promoted neurogenesis after cerebral ischemia/reperfusion in part by inhibiting the Nogo-A–RhoA–ROCK pathway. Here, we examine the hypothesis that CIMT combined with the ROCK inhibitor fasudil further amplifies neurogenesis during stroke recovery.

Methods

Four groups of rats were randomized as follows: Cerebral ischemia-reperfusion (IR), Fasudil, CIMT and CIMT + Fasudil. Seven days after stroke, CIMT and/or intraperitoneal infusion of fasudil were initiated and continued for 3 weeks. The behavioral outcomes and immunohistochemical markers of neurogenesis were quantified.

Results

Compared with other groups, the combination of CIMT with fasudil after IR significantly improved motor and memory function recovery. In addition, BrdU, BrdU/doublecortin and BrdU/GFAP all increased significantly in the brain tissue of the combined treatment group compared to the CIMT or Fasudil group.

Conclusion

These results suggest that the effects of CIMT on neurogenesis are amplified by fasudil during the recovery phase after stroke.

Keywords:

• Constraint-induced movement therapy
• neurogenesis
• cerebral ischemia
• fasudil

Disclosure statement

No potential conflict of interest was reported by the author(s).