Dorsal root ganglion axons facilitate and guide cortical neural outgrowth: In vitro modeling of spinal cord injury axonal regeneration

Article type: Research Article

Authors: Xu, Zi-Xing^a | Albayar, Ahmed^{b; *} | Dollé, Jean-Pierre^b | Hansel, Gisele^b | Bianchini, Justin^b | Sullivan, Patricia Zadnik^c | Cullen, D. Kacy^{b; d} | Smith, Douglas H.^b | Ozturk, Ali K.^c

Affiliations: [a] Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, P.R. China | [b] Center for Brain Injury & Repair, Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA | [c] Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA | [d] Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA

Correspondence: [*] Corresponding author: Ahmed Albayar, MD, Room 283, 220 S33rd St, Philadelphia, PA 19104, USA. Tel.: +1 267 270 7382; E-mail: [email protected].

Abstract: Background:Spinal cord injury (SCI) patients represent a heterogeneous group, with injuries ranging from partial compression to complete transection. Patients with complete injuries are unlikely to exhibit recovery and suffer from paralysis as well as the loss of bowel and bladder function. One treatment option is the formation of a bridge through a lesion site, whereby transplanted cells or biocompatible scaffolds guide the regenerating axons across the site of injury. Moreover, the viability of transplanted dorsal root ganglia (DRGs) into rat spinal cord has been previously demonstrated. Objective:We aim to demonstrate the feasibility of using DRG axons as a bridging tool to help guide the axonal growth of cortical neurons. Methods:Cortical neurons were isolated from embryonic rats and two aggregated populations were cultured at increasing distances in isolation and in a co-culture with DRG explants. Growth rates of the sprouting axons and connections between the two populations were observed over a period of twelve days. Results:DRG explants demonstrated the ability to grow robust axonal connections that can connect two explants separated by up to 10 mm, however, CNAs could not achieve connections in distances greater than 2 mm. The co-culture of CNAs with DRG explants facilitated axonal growth between two populations of CNAs at distances they cannot otherwise traverse. Conclusions:Our findings support the use of DRG axons to facilitate the growth of cortical neurons in a process of axon-facilitated axon regeneration. We believe these results could have implications for the treatment of SCI.

Keywords: Traumatic brain injury (TBI), central nervous system regeneration, spinal cord injury (SCI), dorsal root ganglia (DRG) transplantation, cortical neuron aggregates (CNAs), experimental modeling, axonal guidance, axonal bridging

DOI: 10.3233/RNN-190933

Journal: Restorative Neurology and Neuroscience, vol. 38, no. 1, pp. 1-9, 2020