DENSITY OF CORTICOSPINAL (CS) FIBERS CAUDAL TO A CERVICAL HEMISECTION IN MONKEYS CORREALTES WITH BEHAVIORAL RECOVERY AND BOTH ARE ENHANCED BY ANTI-NOGO-A TREATMENT.

P. Freund (1), T. Wannier (1,2), E. Schmidlin (1) , J. Bloch (3), A. Mir (4), M.E. Schwab (2), E.M. Rouiller (1).

In rats, neutralization of the neurite growth inhibitor Nogo was shown to improve motor recovery from spinal cord lesion. The goal of the present study was to transpose the anti-Nogo strategy to subhuman primates. Macaque monkeys were trained to perform a dexterity task. Then, the monkeys were subjected to a cervical hemisection at C7/C8 level. A subgroup of monkeys was treated over a period of 4 weeks with Nogo antibodies whereas a control antibody was infused in the control group via an osmotic pump. In all monkeys, the hand homolateral to the lesion was impaired and then, over a period of a few weeks, a progressive recovery of dexterity took place, reaching variable levels of performance. Due to the considerable variability of the lesion size and experimental conditions, the data were analyzed by comparing four matched pairs of monkeys, each pair comprising one treated and one control monkey. In three pairs of monkeys subjected to a comparable cervical cord lesion, or even larger in the treated monkey, the recovery of manual dexterity was faster and/or more complete in the anti-Nogo treated animal, as compared to the control animal. In the fourth pair of monkeys, in which the lesion was slightly larger in the control monkey, the recovery of manual dexterity was considerably stronger in the treated monkey. A detailed anatomical investigation was conducted in seven of the above mentioned macaque monkeys. The anterograde tracer BDA was injected in the motor cortex. The lesion completely interrupted the dorsolateral funiculus in five monkeys (three treated and two control), whereas a small contingent was preserved in two control monkeys. CS axonal arbors were detected below the lesion in all, more densely however, in the three treated animals and the partly lesioned control monkeys. All treated monkeys exhibited a full functional recovery for the dexterity task, whereas the control monkey with the complete lesion poorly recovered. In the treated monkeys the recovery was faster than in the controls. These data suggest that the density of CS axonal arbors caudal to the lesion correlates with the level of functional recovery, indicating that reconstruction of the CS tract contributes to the recovery of manual dexterity. Moreover, this mechanism of recovery is enhanced by anti-Nogo treatment.