The effect of lithium and lithium-loaded hyaluronic acid hydrogel applications on nerve regeneration and recovery of mot

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The effect of lithium and lithium‑loaded hyaluronic acid hydrogel applications on nerve regeneration and recovery of motor functions in peripheral nerve injury Atacan Emre Kocman1   · Ilknur Dag2,3   · Tayfun Sengel2   · Erdem Soztutar4   · Mediha Canbek5  Received: 28 February 2020 / Accepted: 9 June 2020 © Accademia Nazionale dei Lincei 2020

Abstract  Functional recovery rates after peripheral nerve injury are quite poor. Studies have focused on the organization of axonal development and the alteration of the microenvironment of the regenerated nerve. It is a frequently used repair method to place a tube to the incision area with tubulization technique and to try increasing the effect by filling the tube with various substances. Hyaluronic acid is a natural polysaccharide, and since it is biodegradable, it makes an ideal biomaterial in peripheral nerve healing. Lithium chloride (LiCl), a Glycogen synthase kinase 3β (GSK3β) inhibitor, is also frequently used in the treatment of bipolar and depressive disorders, but it has strong neuroprotective and antiinflammatory effects. In this study, peripheral nerve injury was induced on the rat sciatic nerve and silicon conduit was placed to this area and the effects of application of LiCl (2.5, 5 and 15 mEq doses) and LiCl (15 mEq)-loaded hyaluronic acid hydrogel in the conduit on peripheral nerve regeneration and improvement of motor functions were investigated. Sciatic nerve index (SFI) was measured at 2nd, 4th, 8th, and 12th weeks for each animal. Histological, microscopic, and morphometrical analyzes were evaluated at the end of the experiment (12th weeks). Our results indicate that topically applied lithium has positive effect after peripheral nerve injury and especially 5 mEq LiCl can increase nerve regeneration in rats. Further studies are needed to discuss the morphological, molecular and mechanical potential of treatment application.

* Ilknur Dag [email protected] 1



Department of Plastic and Reconstructive Surgery, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey

2



Central Research Laboratory Application and Research Center, Eskisehir Osmangazi University, Eskisehir, Turkey

3

Vocational Health Services High School, Eskisehir Osmangazi University, Eskisehir, Turkey

4

Department of Anatomy, Medical Faculty, Yeditepe University, Istanbul, Turkey

5

Department of Biology, Faculty of Science, Eskisehir Osmangazi University, Eskisehir, Turkey



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Rendiconti Lincei. Scienze Fisiche e Naturali

Graphical Abstract

Keywords  Lithium · Hyaluronic acid · Motor function · Nerve regeneration

1 Introductıon Traumatic injury of peripheral nerves is a very common situation and it may cause a loss in motor and sensorial functions (Menorca et al. 2013). Peripheral nervous system (PNS) has a significant regeneration capability contrary to the central nervous system. PNS injury is treated with either two nerve endings were directly attached or an autograft was placed into the injury site (Höke and Brushart 2010; Houschyar e