Exogenous Neuritin Promotes Nerve Regeneration After Acute Spinal Cord Injury in Rats
- 1 July 2016
- journal article
- research article
- Published by Mary Ann Liebert Inc in Human Gene Therapy
- Vol. 27 (7), 544-554
- https://doi.org/10.1089/hum.2015.159
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.Keywords
This publication has 52 references indexed in Scilit:
- Local and Remote Growth Factor Effects after Primate Spinal Cord InjuryJournal of Neuroscience, 2010
- Neuritin Mediates Nerve Growth Factor–Induced Axonal Regeneration and Is Deficient in Experimental Diabetic NeuropathyDiabetes, 2008
- NGF mRNA is expressed in the dorsal root ganglia after spinal cord injury in the ratExperimental Neurology, 2007
- Characterization of the expression of the hypoxia‐induced genes neuritin, TXNIP and IGFBP3 in cancerFEBS Letters, 2006
- Combined Treatment with Neurotrophin-3 and LSD Facilitates Behavioral Recovery from Double-Hemisection Spinal Injury in Neonatal RatsJournal of Neurotrauma, 2006
- Coordinated Motor Neuron Axon Growth and Neuromuscular Synaptogenesis Are Promoted by CPG15 In VivoNeuron, 2005
- Neuronal plasticity after spinal cord injury: identification of a gene cluster driving neurite outgrowthThe FASEB Journal, 2004
- Defective HSV-1 Vector Expressing BDNF in Auditory Ganglia Elicits Neurite Outgrowth: Model for Treatment of Neuron Loss Following Cochlear DegenerationHuman Gene Therapy, 1996
- Incidence of traumatic spinal cord lesionsJournal of Chronic Diseases, 1975
- EXPERIMENTAL OBSERVATIONS OF CONCUSSION AND CONTUSION OF THE SPINAL CORDAnnals of Surgery, 1953