Functional recovery after monoclonal antibody IN-1 treatment in adult rats with sensorimotor cortex lesions

Injury in the adult CNS is characterized by limited neuroanatomical repair and often results in chronic functional deficits. This limited ability for repair is in part attributed to barriers in the extracellular matrix that prevent the remodeling of neuroanatomical pathways. One such obstacle is the expression of Nogo-A at the cell surface of oligodendrocytes. Previous studies have shown that the neutralization of Nogo-A with monoclonal antibody IN-1 (mAb IN-1) results in significant behavioral recovery after pyramidotomy and ischemic stroke. This dissertation project addresses the functional outcome in adult animals after sensorimotor cortex lesions and treatment with mAb IN-1.Animals were tested in two skilled behavioral tasks to assess forelimb reaching, digit grasping and forelimb placement. Treatment with mAb IN-1 in adult animals after sensorimotor cortex lesions resulted in significant recovery from forelimb reaching and placement deficits as compared to control treatment animals. Based on previous studies, we postulated that the remodeling of the corticospinal tract might be one mechanism of recovery hence, these same animals were injected with a neuroanatomical tracer in the motor cortex opposite to the damaged hemisphere. The results from anatomical analysis demonstrate a significant increase in the number of corticospinal fibers projecting into deafferented alpha-motoneuron pool in the cervical spinal cord. Furthermore, behavioral recovery correlated with corticospinal tract remodeling. In a separate group of animals, intracortical micro stimulation of the intact motor cortex confirmed the presence of a functional pathway in facillitating movements of the injured forelimb. This observed functional reorganization could be important for recovery of motor functions after cortical damage resulting from stroke, traumatic brain injury, multiple sclerosis, or spinal cord injury. Ultimately, strategies that include treatment with mAb IN-1 or blockade of Nogo-A will enhance recovery after CNS injury in humans.