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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F18%3A00101399" target="_blank" >RIV/00216224:14110/18:00101399 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/GA16-08508S" target="_blank" >GA16-08508S: Zvýšení endogenního regeneračního programu a jeho aktivace zprostředkovaná cytokiny/chemokiny v neuronech ganglií bez spojení s poškozeným nervem</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů