Abstract 3573: Successful Regeneration After Experimental Stroke by G-CSF is not Further Enhanced by Constraint-Induced Movement Therapy

Abstract

Background and Purpose Both application of granulocyte-colony stimulating factor (G-CSF) and constraint-induced movement therapy (CIMT) have been shown to improve recovery after experimental stroke. The aim of the present study was to determine whether concurrent or sequential combination of both therapies will further enhance the therapeutic benefit and whether specific modifications in the abundance of various neurotransmitter receptors do occur. Methods Adult male Wistar rats were subjected to photothrombotic ischemia and assigned to the following treatment groups (n=20 each): (1) ischemic control (saline); (2) CIMT (CIMT between post-stroke day 2 and 11; (3) G-CSF (10μg/kg G-CSF daily between post-stroke day 2 and 11 (4), combined concurrent group (CIMT plus 10μg/kg G-CSF daily between post- stroke day 2 and 11; (5) combined sequential group (CIMT between post-stroke day 2 and 11 and 10μg/kg G-CSF daily between post-stroke day 12 and 21, respectively). Rats were functionally tested before and up to 4 weeks after ischemia. Quantitative receptor autography was performed for NMDA, AMPA and GABAA receptors. Results Significant improvement of functional outcome was seen in all groups treated with G-CSF alone and in either combination with CIMT, while CIMT alone failed to enhance recovery. Infarct sizes and remaining cortical tissue did not differ in the various treatment groups. Failure of significant benefit in the CIMT group was associated with a shift towards inhibition in perilesional and remote cortical regions. Conclusions Our findings unveil G-CSF as the key player for enhanced recovery after experimental stroke, preventing a shift towards inhibition as seen in the solitary CIMT group.