Transneuronal delivery of hyper-interleukin-6 enables functional recovery after severe spinal cord injury in mice

Abstract Spinal cord injury (SCI) often causes severe and permanent disabilities due to the regenerative failure of severed axons. Here we report significant locomotor recovery both hindlimbs after a complete spinal crush. This is achieved by unilateral transduction cortical motoneurons with an AAV expressing hyper-IL-6 (hIL-6), potent designer cytokine stimulating JAK/STAT3 signaling axon regeneration. We find collaterals these AAV-transduced projecting serotonergic neurons in sides raphe nuclei. Hence, facilitates axonal transport release hIL-6 at innervated brain stem. Therefore, this transneuronal delivery promotes regeneration corticospinal raphespinal fibers injury, latter being essential for hIL-6-induced functional recovery. Thus, enables stimulation deep stem that are otherwise challenging access, yet highly relevant SCI.