The effects of intracortical endothelin-1 injections on skilled forelimb use: implications for modelling recovery of function after stroke.

ABSTRACT

Different methods of inducing experimental brain lesions can result in distinct neuropathological sequelae. This could be of consequence in attempts to establish animal models of recovery of function following stroke, as differences in the progression of experimental lesion pathology may have an impact on the magnitude and rate of recovery of function observable with any particular lesioning method. In the present study, a novel method of producing a focal ischaemic lesion by intracortical microinjection of endothelin-1 (ET-1) was compared with excitotoxic (microinjection of quinolinic acid) and mechanical (aspiration) lesioning procedures. Lesions were unilateral and were targeted at the forelimb representation zone in sensorimotor cortex. It was found that all three types of lesion had an essentially identical effect with regard to reaching accuracy in a paw-reaching task. All lesioned animals displayed a similar, significant long-term deficit in reaching accuracy and limited degree of recovery relative to sham animals. Off-line analysis of the performance of animals during post-lesion week 9 indicated that animals in each lesion group also displayed a similar deficit. The current results suggest that the spontaneous behavioural consequences of a unilateral lesion of FL in the rat appear to be independent of the nature of lesion production. However, the increased face validity of an ET-1-induced lesion, coupled with the ease of control of lesion placement and extent offered by this technique make for a potentially important animal model for research into drug effects on recovery of function following stroke.