The effects of willed movement on the extracellular signal-regulated kinase and cAMP response element binding protein pathway following focal cerebral ischemia

Abstract

Objective To explore the effects of willed movement on neurological performance and the extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) pathway in rats following focal cerebral ischemia. Methods Reversible middle cerebral artery occlusion was induced in 144 male Sprague-Dawley rats using intraluminal sutures, and they were randomly divided into a control group, a swimming exercise group, an environment modification group, and a willed movement group. The observation time points were at 7, 15 and 30 days after reperfusion. A behavioral test was performed to evaluate any neurological deficiency. Reverse transcription PCR (RT-PCR) and immunofluorescence were used to detect the ERK and CREB responses in terms of mRNA and phosphorylated ERK (pERK) and phosphorylated CREB (pCREB) protein in the peri-ischemic brain tissue. Results The climbing frequency of the willed movement group was significantly higher than that of the environment modification group. Three days after reperfusion the neurological deficit scores of all groups began to decrease, and that of the willed movement group had decreased significantly more than in the other three groups at all time points. ERK/CREB mRNA and pERK and pCREB protein expression were dramatically up-regulated in the willed movement group at 7, 15 and 30 days after reperfusion, significantly more than in the other three groups. Conclusions Willed movement may promote motor recovery by up-regulating and activating the ERK/CREB pathway following focal cerebral ischemia. Key words: Brain ischemia; Exercise therapy; Willed movement; Signal pathways