Neuroinflammatory regulations of regenerative program in the dorsal root ganglia neurons non-associated with injured nerve

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Authors

DUBOVÝ Petr HRADILOVÁ SVÍŽENSKÁ Ivana KLUSÁKOVÁ Ilona BRÁZDA Václav JOUKAL Marek

Year of publication 2018
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Citation
Description We found earlier that unilateral sciatic nerve injury can induce inflammatory reactions bilaterally not only in the dorsal root ganglion (DRG) neurons associated with L4-L5 spinal cord segments but also in remote cervical DRG. This systemic neuroinflammatory reaction of DRG neurons can be related with their pro-regenerative state after peripheral nerve injury. To verify our hypothesis, we investigated axon regeneration distal to the rat ulnar nerve crush after prior sciatic nerve injury, and after intrathecal application of IL-6 or AG490 inhibitor of JAK2 in comparison to vehiculum. A role of IL-6 in activation of pro-regenerative state of DRG neurons was also tested in IL-6 -/- mice. We found that sciatic nerve lesion for 7 days increased the distance of regenerated axons after the ulnar nerve crush. In addition, simultaneous intrathecal application of IL-6 with the ulnar nerve crush extended regenerated axons, too. In contrast, inhibition of STAT3 phosphorylation by JAK2 resulted in significantly reduced lengths of regenerated axon. A regeneration of axons distal to the ulnar nerve crush after prior sciatic nerve injury was significantly reduced in IL-6 -/- mice. The results presented here confirmed that unilateral sciatic nerve injury can induce pro-regenerative state of the cervical DRG neurons non-associated with injured nerve. This reflects a systemic reaction of the DRG neurons alongside neuroaxis to unilateral nerve injury mediated by IL-6 released into the paraspinal intrathecal space.
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