Therapeutic Effect of Neurotrophin-3 Treatment in an Injectable Collagen Scaffold Following Rat Spinal Cord Hemisection Injury

Abstract

Background. Spinal cord injury (SCI) presents to the clinic as complete, incomplete or compressive. SCI patients also display varying quantities of spinal cord tissue damage or loss. One theory proposed to repair the injured spinal cord and regain motor control is to regenerate axons through the lesion site. Current methods proposed to increase neuroregeneration following SCI include; preserving spared neuronal tissue, increasing axonal regeneration, reducing inflammation, reducing glial scar formation and methods aimed at bridging the lesion gap to facilitate the transmittance of physical cues and provide a platform for neuronal sprouting and functional recovery. Objective. This study was designed to quantify the impact of a local injectable in situ forming hydrogel reservoir therapy following rat hemisection SCI. Method. Our group investigated the effect of hydrogel only treatment following SCI in addition to hydrogels loaded with a neuronal growth factor, Neurotrophin-3 (NT-3), immediately following SCI. Functional recovery, assessed by Basso Beattie Bresnahan (BBB), and local healing mechanism, including neuronal regeneration, neuronal survival, glial scar formation, inflammation, astrocytosis, and collagen deposition were investigated one and six weeks post-surgery. Results. Delivery of an injectable hydrogel increased functional recovery, reduced inhibitory glial scarring and reducing inflammation at the injury site. Similarly hydrogel + NT-3 delivered directly into the injury site reduced glial scarring and collagen deposition resulting in increased neuronal survival across the lesion site. Conclusion. This study represents a novel and effective therapy combining growth factor and a biomaterial based therapy following SCI.

Distinct Glycosylation Responses to Spinal Cord Injury in Regenerative and Nonregenerative Models

“… 30 A previous study by our group demonstrated that collagen hydrogel reduced the amount of ionized calcium-binding adaptor molecule 1 (Iba-1) and neuron-glial antigen 2 (NG2) chondroitin sulfate proteoglycan (CSPG)-positive staining and led to improved motor function following SCI. 31 Considering these observed effects, we asked whether the glycosylation profile of the tissue may also be influenced by treatment with a biomaterial. From recent in vitro studies, it is clear that coupling glycans and collagen can influence populations of neural cells: either by driving neuronal differentiation of immortalized cell lines 32 or by influencing the glycosylation status of primary neural cells, 33 and this strategy will warrant investigation in SCI.…”

“…In this study, we use a collagen hydrogel for the treatment of SCI in the rat. Although collagen is a minor constituent of the CNS extracellular matrix, 34 it is well tolerated, not eliciting any obvious foreign body response, 31 , 35 , 36 and has been approved by FDA for peripheral nerve treatments. 37 Being a fibrillar protein, collagen can be manipulated to provide aligned surface guidance for migrating cells or growing axons.…”

In-Silico Analysis of the NT-3 (Neurotrophin-3) Protein Expressed by the NTF-3 (Neurotrophic Factor-3) Gene in Homo sapiens

“…NTF-3 is the gene that encodes the NT-3 protein [8], and function as a neurotrophic factor that is responsible for enhancing the development of neuron function [9]. The NT-3 protein can increase the regeneration of damaged neurons by binding to the ERBb gene [10]. The NT-3 protein plays an important role in controlling the number of neurons and the growth of dendrites [11].…”

A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

“…Several studies have demonstrated the great potential of collagen-based scaffolds as cell carriers and bridging material in numerous experimental animal models of CNS. The implantation has been demonstrated to be safe and has induced significant repair in SCI by increasing neurons and inhibiting glial scar formation [ 27 , 28 , 29 ]. Hence, collagen has become one of the most favored natural material sources for treating SCI.…”