The effect of lithium and lithium-loaded hyaluronic acid hydrogel applications on nerve regeneration and recovery of motor functions in peripheral nerve injury

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.