Unilateral ischemic sensorimotor cortical damage induces contralesional synaptogenesis and enhances skilled reaching with the ipsilateral forelimb in adult male rats.

Unilateral damage to the forelimb representation area of the sensorimotor cortex (SMC) results in a compensatory reliance on the unimpaired (ipsilateral to the lesion) forelimb as well as reorganization of neuronal structure and connectivity in the contralateral motor cortex. Recently, male rats with unilateral electrolytic SMC lesions were found to have enhanced skilled reaching performance with the ipsilesional forelimb compared with sham-operated controls. The present study was performed to determine whether these behavioral findings are replicable using an ischemic lesion and whether there is a link between the enhanced learning and synaptogenesis in motor cortical layer V opposite the trained limb and lesion, as assessed using stereological methods for light and electron microscopy. Rats were given a sham operation or an endothelin-1 (ET-1) induced ischemic SMC lesion. They were then trained for 20 days on a skilled reaching task with the unimpaired limb or received control procedures. As with previous findings using electrolytic lesions, rats with unilateral ischemic SMC lesions performed significantly better using the unimpaired forelimb than did sham-operates. Lesions, but not training, significantly increased the total number of motor cortical layer V synapses per neuron as well as the number of perforated and multisynaptic bouton (MSB) synapses per neuron compared with shams. Thus, in addition to a net increase in synapses, the improved reaching ability was coupled with an increase in synapse subtypes that have previously been linked to enhanced synaptic efficacy. The failure to induce synaptogenesis in layer V with reach training alone is in contrast to previous findings and may be related to training intensity.

Importance of behavioral manipulations and measures in rat models of brain damage and brain repair.

The relevance of careful behavioral measures and manipulations in animal research on neural plasticity and brain damage has become increasingly clear. Recent research in adult rats indicates that an understanding of neural restructuring after brain damage requires an understanding of how it is influenced by postinjury behavioral experiences. Other research indicates that optimizing pharmacological and other treatments for brain damage may require their combination with rehabilitative training. Assessing the efficacy of a treatment approach in animal models requires the use of sensitive behavioral measures of functional outcome. In research on restorative plasticity after brain damage, procedures for handling and housing rats should promote the quality of behavioral measures and manipulations.