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Dexmedetomidine to Help Nerve Regeneration in a Rat Sciatic Nerve Injury Model.

ABSTRACT: Several studies have shown that dexmedetomidine (DXM), a selective ?2-adrenoceptor agonist, also has neuroprotective effects. However, its effect on impaired peripheral nerve regeneration has not been studied.Forty-five Sprague-Dawley rats were randomly assigned to three groups: group 1 (control SHAM), group 2 (sciatic nerve injury?+?normal saline), and group 3 (sciatic nerve injury?+?DXM). The rats of group 3 were subdivided into the following three groups: DXM 0.5, 6, and 20??g·kg-1 (groups 3A, 3B, and 3C, resp.). The sciatic nerve injury was assessed for nerve regeneration at 2 and 6 weeks.There were no differences between groups 2 and 3 in their sciatic functional index (SFI) values or histological findings at 2 weeks postinjury. However, SFI differences were statistically significant at 6 weeks postinjury in group 3. The gross findings with H&E staining showed that the number of axons was higher in group 3 than in group 2. There was no histological difference according to the DXM concentration.The coincidental functional and histological assessment results of this study suggest that DXM for 6 weeks positively affects damaged peripheral nerves.

SUBMITTER: Jeong W

PROVIDER: S-EPMC5745707 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Dexmedetomidine to Help Nerve Regeneration in a Rat Sciatic Nerve Injury Model.

Jeong Wook W Kung Hsichiang H Cheng Chia Chi CC Lim Changwoo C Jung Min Jung MJ Lee Jaeho J Kim Doo Sik DS Shin Yusom Y

Pain research & management 20171213

<h4>Background</h4>Several studies have shown that dexmedetomidine (DXM), a selective <i>α</i>2-adrenoceptor agonist, also has neuroprotective effects. However, its effect on impaired peripheral nerve regeneration has not been studied.<h4>Materials and methods</h4>Forty-five Sprague-Dawley rats were randomly assigned to three groups: group 1 (control SHAM), group 2 (sciatic nerve injury + normal saline), and group 3 (sciatic nerve injury + DXM). The rats of group 3 were subdivided into the follo ...[more]

PMID: 29527118

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Project description:BackgroundPeripheral nerve injuries are accompanied by inflammatory reactions, over-activation of which may hinder recovery. Among pro-inflammatory pathways, inflammasomes are one of the most potent, leading to release of active IL-1β. Our aim was to understand how inflammasomes participate in central inflammatory reactions accompanying peripheral nerve injury.MethodsAfter axotomy of the sciatic nerve, priming and activation of the NLRP3 inflammasome was examined in cells of the spinal cord. Regeneration of the nerve was evaluated after coaptation using sciatic functional index measurements and retrograde tracing.ResultsIn the first 3 days after the injury, elements of the NLRP3 inflammasome were markedly upregulated in the L4-L5 segments of the spinal cord, followed by assembly of the inflammasome and secretion of active IL-1β. Although glial cells are traditionally viewed as initiators of neuroinflammation, in this acute phase of inflammation, inflammasome activation was found exclusively in affected motoneurons of the ventral horn in our model. This process was significantly inhibited by 5-BDBD, a P2X4 receptor inhibitor and MCC950, a potent NLRP3 inhibitor. Although at later time points the NLRP3 protein was upregulated in microglia too, no signs of inflammasome activation were detected in these cells. Inhibition of inflammasome activation in motoneurons in the first days after nerve injury hindered development of microgliosis in the spinal cord. Moreover, P2X4 or inflammasome inhibition in the acute phase significantly enhanced nerve regeneration on both the morphological and the functional levels.ConclusionsOur results indicate that the central reaction initiated by sciatic nerve injury starts with inflammasome activation in motoneurons of the ventral horn, which triggers a complex inflammatory reaction and activation of microglia. Inhibition of neuronal inflammasome activation not only leads to a significant reduction of microgliosis, but has a beneficial effect on the recovery as well.

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Dexmedetomidine to Help Nerve Regeneration in a Rat Sciatic Nerve Injury Model.

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Dexmedetomidine to Help Nerve Regeneration in a Rat Sciatic Nerve Injury Model.

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