Dynamic induction of the myelin‐associated growth inhibitor Nogo‐A in perilesional plasticity regions after human spinal cord injury

The myelin-associated inhibitor Nogo-A (Reticulon 4, RTN4) restricts axonal outgrowth, plasticity, and neural circuitry formation in experimental models of spinal cord injury (SCI) and is targeted in clinical interventions starting treatment within 4 weeks post-SCI. Specifically, Nogo-A expressed by oligodendroglia restricts compensatory neurite sprouting. To interrogate the hypothesis of an inducible, lesion reactive Nogo-A expression over time, we analyzed the spatiotemporal Nogo-A expression at the spinal lesion core (region of tissue necrosis and axonal damage/pruning) and perilesional rim (region of plasticity formation). Spinal cord specimens of SCI subjects (n = 22) were compared to neuropathologically unaltered controls (n = 9). Nogo-A expression was investigated ranging from acute (0-3 days), early subacute (4-21 days), late subacute (22-90 days) to early chronic-chronic (91 days to 1.5 years after SCI) stages after SCI. Nogo-A expression in controls is confined to motoneurons in the anterior horn and to oligodendrocytes in gray and white matter. After SCI, the number of Nogo-A