Intrathecal delivery of IL-6 reactivates the intrinsic growth capacity of pyramidal cells in the sensorimotor cortex after spinal cord injury.

We have previously demonstrated the growth-promoting effect of intrathecal delivery of recombinant rat IL-6 immediately after corticospinal tract (CST) injury. Our present study aims to further clarify whether intrathecal delivery of IL-6 after CST injury could reactivate the intrinsic growth capacity of pyramidal cells in the sensorimotor cortex which project long axons to the spinal cord. We examined, by ELISA, levels of cyclic adenosine monophosphate (cAMP), adenylyl cyclase (AC, which synthesizes cAMP), phosphodiesterases (PDE, which degrades cAMP), and, by RT-PCR, the expression of regeneration-associated genes in the rat sensorimotor cortex after intrathecal delivery of IL-6 for 7 days, started immediately after CST injury. Furthermore, we injected retrograde neuronal tracer Fluorogold (FG) to the spinal cord to label pyramidal cells in the sensorimotor cortex, layers V and VI, combined with βIII-tubulin immunostaining, then we analyzed by immunohistochemisty and western blot the expression of the co-receptor gp-130 of IL-6 family, and pSTAT3 and mTOR, downstream IL-6/JAK/STAT3 and PI3K/AKT/mTOR signaling pathways respectively. We showed that intrathecal delivery of IL-6 elevated cAMP level and upregulated the expression of regeneration-associated genes including GAP-43, SPRR1A, CAP-23 and JUN-B, and the expression of pSTAT3 and mTOR in pyramidal cells of the sensorimotor cortex. In contrast, AG490, an inhibitor of JAK, partially blocked these effects of IL-6. All these results indicate that intrathecal delivery of IL-6 immediately after spinal cord injury can reactivate the intrinsic growth capacity of pyramidal cells in the sensorimotor cortex and these effects of IL-6 were partially JAK/STAT3-dependent.