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BDNF infusion into the sensorimotor cortex promotes sprouting of inact corticospinal fibers within the spinal cord after a unilateral pyramidal lesion Khodarahmi, Kourosh

Abstract

More than half of all spinal cord injuries are anatomically incomplete, yet many of these result in complete loss of motor function below the level of injury. One approach to enhance functional recovery is to exploit spared CNS axons (that extend past the point of injury) to sprout and connect to potential targets. We have previously found that application of the neurotrophin; BDNF, to the sensory-motor cortex stimulates expression of regeneration associated genes such as GAP-43, and Tαl tubulin, and results in enhanced sprouting of injured corticospinal fibers rostral to the site of injury. Here, we investigated whether infusion of BDNF into the intact sensorimotor cortex induces sprouting of undamaged corticospinal fibers into denervated cervical spinal cord. We also studied the effect of this treatment using several behavioral tasks: gait analysis, forelimb inhibition during swimming, and food pellet reaching task. The results show that BDNF infusion into the intact sensorimotor cortex subsequent to a unilateral pyramidal lesion increases (3.2 fold) the sprouting of intact corticospinal fibers into the denervated, contralateral grey matter at the lumbar level of the spinal cord when compared with vehicle treated rats. This effect was not seen at the cervical level of the spinal cord. Functionally, unilateral pyramidal injury of corticospinal axons significantly increased toe spread of the contralateral denervated forelimb and hindlimb when compared to the uninjured side. BDNF treatment showed a recovery to presurgical levels. Testing of fine motor control with a food pellet reaching task demonstrated deficits in the impaired forelimb but did not show any improvement due to BDNF treatment.

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