Nerve regeneration in chitosan conduits and in autologous nerve grafts in healthy and in type 2 diabetic Goto–Kakizaki rats

Abstract

Knowledge about nerve regeneration after nerve injury and reconstruction in appropriate diabetic animal models is incomplete. Short-term nerve regeneration after reconstruction of a 10-mm sciatic nerve defect with either a hollow chitosan conduit or an autologous nerve graft was investigated in healthy Wistar and diabetic Goto-Kakizaki (GK) rats. After 21 days, axonal outgrowth, the presence of activated and apoptotic Schwann cells and the thickness of the formed matrix in the conduits were measured. In general, nerve regeneration was superior in autologous nerve grafts. In chitosan conduits, a matrix, which was thicker in diabetic rats, was formed and was positively correlated with length of axonal outgrowth. Axonal outgrowth in conduits and in nerve grafts extended further in diabetic rats than in healthy rats. There was a higher percentage of activating transcription factor 3 (ATF3)-immunostained cells in nerve segments from healthy rats than in diabetic rats after autologous nerve graft reconstruction. In chitosan conduits, more cleaved caspase 3-stained Schwann cells were generally observed in the matrix from the diabetic rats than in healthy rats. However, there were fewer apoptotic cells in the distal segment in diabetic rats reconstructed with a chitosan conduit. Preoperative glucose levels were positively correlated with axonal outgrowth after both reconstruction methods. Axonal regeneration was better in autologous nerve grafts than in hollow chitosan conduits and was enhanced in diabetic GK rats compared to healthy rats after reconstruction. This study provides insights into the nerve regeneration process in a clinically relevant diabetic animal model.

Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides

“…The described procedures have been performed in different previous studies and are routine procedures to analyze the regenerating conditions short-term after peripheral nerve reconstruction with tubular grafts [7, 10, 11, 14]. …”

“…Activated Schwann cells, defined as ATF-3 stained Schwann cells [10, 11, 14], were observed in the formed regenerative matrix in generally small proportions (median values 6.0–16.8%). The values displayed no significant differences between the groups (Table 2; it should be recognized that only few matrices were available for immunostaining in the middle of the conduit, particularly in the hCNG-I healthy samples).…”

“…This is of specific importance also for new nerve guides. Recently, we showed in short-term investigations in diabetic Goto-Kakizaki (GK) rats, with moderately increased and clinically relevant blood glucose levels, sufficient nerve regeneration through chitosan nerve guides and autologous nerve grafts bridging short and critical length sciatic nerve defects of up to 15 mm [10, 11]. Consequently, our first objective in the current study was to evaluate if sufficient nerve regeneration could also be observed in short-term evaluation in healthy Wistar and in diabetic GK rats after a delayed nerve reconstruction bridging the longer nerve defect (15 mm) with two different types of chitosan nerve guides that earlier have demonstrated their beneficial effect after acute nerve reconstruction [10].…”

Local Administration of Methylprednisolone Laden Hydrogel Enhances Functional Recovery of Transected Sciatic Nerve in Rat

“…Functional recovery of the nerve was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale for rat hind limb motor function [16]. Although BBB is widely used to assess functional recovery in spinal cord injured animals, however, it has been demonstrated that it could be most useful in assessment of never repair processes in peripheral nerve injuries [17].…”

Effect of Local Delivery of GDNF Conjugated Iron Oxide Nanoparticles on Nerve Regeneration along Long Chitosan Nerve Guide

“…Chitosan is a polysaccharide derived from chitin, it is biocompatible, and it can promote glial cells survival and neurite outgrowth [8][9][10]. It has been shown that hollow chitosan tube can be effective as autologous nerve graft for bringing 10-mm gap in rat sciatic nerve model [7,11,12]. In order to increase the performance of chitosan tube for long defect repair; here, we filled the tube with a hydrogel, called NVR gel, composed mainly by hyaluronic acid and laminin.…”