Highlights
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Active peptide OM-LV20 can promote the repair of spinal cord injury (SCI). •
OM-LV20 can significantly improve the recovery of motor function of the hindlimb in rats with traumatic SCI. •
Administration of OM-LV20 increased the number of surviving neuron bodies. •
OM-LV20 might play a neuroprotective role by balancing the redox system in the body.
Abstract
At present, there are no satisfactory therapeutic drugs for the functional recovery of spinal cord injury (SCI). We previously identified a novel peptide (OM-LV20) that accelerated the regeneration of injured skin tissues of mice and exerts neuroprotective effects against cerebral ischemia/reperfusion injury in rats. Here, the intraperitoneal injection of OM-LV20 (1 μg/kg) markedly improved motor function recovery in the hind limbs of rats with traumatic SCI, and further enhanced spinal cord repair. Administration of OM-LV20 increased the number of surviving neuron bodies, as well as the expression levels of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB). In the acute stage of SCI, OM-LV20 treatment also increased superoxide dismutase and glutathione content but decreased the levels of malonaldehyde and nitric oxide. Thus, OM-LV20 significantly promoted structural and functional recovery of SCI in adult rats by increasing neuronal survival and BDNF and TrkB expression, and thereby regulating the balance of oxidative stress. Based on our knowledge, this research is the first report on the effects of amphibian-derived peptide on the recovery of SCI and our results highlight the potential of peptide OM-LV20 administration in the acceleration of the recovery of SCI.
Introduction
Traumatic spinal cord injury (SCI) often results in severe nerve defects and dysfunction due to secondary injury and limited self-repair ability of the central nervous system [1]. Patients with SCI often have different degrees of motor, sensory, and autonomic dysfunction, which can be life-threatening [2]. These factors not only result in serious physical and psychological harm, but also cause huge economic burden to the patients, their families, and society as a whole [2].
After SCI, a series of primary and secondary pathological changes, such as ischemia and anoxia, free radical production, and lipid peroxidation, lead to neuronal apoptosis and necrosis. In the acute phase of injury, the body produces the oxidative stress response, which aggravate tissue damage and further deteriorate the structure and function of SCI [3]. At present, however, there is no specific drug treatment to solve these issues [4]. The steroid drug methylprednisolone (MPED), which is widely used in the treatment of SCI, exhibits a better anti-inflammatory effect when used in large doses in the early stage of injury, but its side effects and therapeutic results have been questioned [5]. Therefore, the development of new drugs to promote SCI repair and recovery is critical.
Peptides demonstrate high activity, high specificity, safety, low cost, and easy production [6,7]. A growing number of active peptides have also been identified, including antimicrobial, antioxidant, analgesic, wound-healing, and anti-gout peptides [[8], [9], [10], [11], [12], [13], [14], [15]]. We previously identified a peptide OM-LV20 from amphibian skin secretions, and functional results indicated that OM-LV20 accelerated the recovery of skin in mice and exerts neuroprotective effects on cerebral ischemia reperfusion injury in rats [16]. This showed that OM-LV20 has a certain contribution to wound repair, especially nerve wound repair. In this research, the application of OM-LV20 improved the microenvironment of the injured spinal cord and promoted motor function recovery of the hind limbs of rats, in addition, OM-LV20 protected the survival of neurons and increased levels of neuroprotective factors. The effects might be related to the balance of redox system in vivo. Therefore, this study confirmed that the active peptide OM-LV20 could be used in the treatment of rat SCI injury, thus providing a new template for the development of candidate drugs to promote SCI repair.
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Section snippets
Synthesis of OM-LV20
OM-LV20 (LVGKLLKGAVGDVCGLLPIC) was artificially synthesized using solid phase synthesis and commercially provided by Wuhan Bioyeargene Biotechnology Co. Ltd (Wuhan, China) with a purity of >95%.
Animals
Adult Sprague-Dawley rats (female, 230–250 g, 8–9-weeks old) used in this study were provided by the Hunan SJA Laboratory Animal Co., Ltd (China) (SYXK (Yunnan) K2015-0002). The rats were housed individually in cages with free access to water and food. The animals were acclimatized to the environment for
OM-LV20 improved hind limb motor function and reduced secondary injury of spinal cord tissue in SCI rats
During the 4-week observation period, the BBB scoring method was used to evaluate motor function recovery in SCI rats and number of deaths were also recoded. There were 6, 6, 10, 10, 10, 11, and 9 surviving rats in the normal, sham-operated, saline, MPED, OM-LV20 (10 ng/kg), OM-LV20 (100 ng/kg), and OM-LV20 (1 μg/kg) groups, respectively. From the operation to 4 weeks after, hind limb motor function in the SCI group recovered gradually, but not fully. In the first week after SCI, hind limb
Discussion
SCI can lead to lifelong disability and cause huge economic costs to society [17]. Although basic experimental and clinical research have brought some progress to the research of this disease, up to this point, there is still no enough effective drug to treat it [18]. Therefore, developing new candidate drugs for the treatment of SCI and reducing the complications of SCI is one of the hot topics in the scientific community.
After the acute phase of SCI, a local glial scar gradually develops,
Declaration of competing interest
The authors declare no competing financial interest.
Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (81760648), Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation (2019FE001 (−162), 2019FE001 (−183), and 2019FE001 (−206)), and Applied Research Foundation of Diagnosis and Treatment Center of Nervous System Diseases of Yunnan Province (ZX2019-03-05). Scientific Research Fund Projects from Department of Education of Yunnan Province (2021J0205).
1
These two authors contributed equally to this work.View full text
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