Exogenous Neuritin Promotes Nerve Regeneration After Acute Spinal Cord Injury in Rats

Abstract

Insufficient local levels of neurotrophic factor after spinal cord injury (SCI) are the leading cause of secondary injury and limited axonal regeneration. Neuritin belongs to a family of neurotrophic factors that promote neurite outgrowth, maintain neuronal survival, and provide a favorable microenvironment for the regeneration and repair of nerve cells after injury. However, it is not known whether the exogenously applied neuritin protein has a positive effect on nerve repair after SCI. This was investigated in the present study using purified human recombinant neuritin expressed in and purified from Pichia pastoris, which was tested in a rat SCI model. A recombinant neuritin concentration of 60 μg/ml induced the recovery of hind limb motor function and stimulated nerve regeneration in rats with SCI. Continuous administration of neuritin at this dose at an early stage after SCI inhibited poly ADP ribose polymerase (PARP) protein degradation and decreased neuronal apoptosis. In addition, during the critical postinjury period of axonal regeneration, exogenous neuritin treatment increased the expression of neurofilament 200 and growth-associated protein 43 in the damaged tissue, which was associated with the restoration of hind limb movement. These results suggest that neuritin creates an environment that promotes nerve cell survival and neurite regeneration after SCI, which contribute to nerve regeneration and the recovery of motor function.

Recombinant hNeuritin Promotes Structural and Functional Recovery of Sciatic Nerve Injury in Rats

“…Neuritin overexpression induces the recovery of crushed optic nerve in mouse (Sharma et al, 2015). We recently showed that recombinant Neuritin protects neurons against apoptosis following spinal cord injury (Gao et al, 2016). In the present study, we investigated whether Neuritin can restore nerve structure and function in a rat model of sciatic nerve injury.…”

Functions and the related signaling pathways of the neurotrophic factor neuritin

“…where they suggested that neuritin created an environment that promoted nerve cell survival and neurite regeneration after SCI, thus contributing to nerve regeneration and recovery of motor function [27] . Besides spinal cord injury, results obtained by Zhao et al suggest that soluble neuritin secreted by astrocytes promoted the recovery of injured hippocampal neurons via adherance to the surface of neurons in ischemic brains [28] .…”

miR‑199a decreases Neuritin expression involved in the development of Alzheimer's disease in APP/PS1 mice

“…Neuritin promotes neurite growth and synaptogenesis in hippocampal and cortical neurons (4,5), and is related to the recovery from nerve injury and learning memory (6)(7)(8). It has further been found that recombinant Neuritin (9) improves nerve regeneration following acute spinal cord injury (10) and sciatic nerve injury in rats (11).…”