| Background:Central nervous system (CNS), the main part of the nervous system, is constituted by brain and spinal cord and is mainly responsible for information processing, transmission and storage. Spinal cord that is located in spinal vertebrae composed of spine and protected by spine, is not only the lower extension of central nervous system, but also the primary reflex center of simple human activities. Autonomic nerves and a part of parasympathetic nerve originated from spinal cord lateral horn or the equivalent portions of lateral horn, play an important role in the transmission of information between the peripheral nerves and the brain. Spinal cord hasfour functions, including reflection, conduction,movement and adjustment. Various sensory afferent impulses from limbs, trunk, and the most visceral spread to brain center through the uplink fiber bundles of the spinal cord, where a more advanced comprehensive analysis does. Impulses sent by the brain also must be pass the downlink fiber bundles of spinal cord white matter to adjust the trunk, limbs, skeletal muscle and visceral physiological activities. Spinal cord injury (SCI) as the most serious complications of spine injury is a common high disabling and fatal neurological trauma. Trauma, inflammation, cancer and so on cause the shift of the vertebral body or spinal bone chips protrude, as a result of the damage of spinal cord or cauda equine at different degrees, eventually resulting in a variety of sensory, motor, autonomic and sphincter dysfunction, as well as the corresponding changes in muscle tone and abnormal pathological reflection. The above pathological changes will lead to sensory, motor disorders, reflex dysfunction and other symptoms, ultimately leadingto many organ dysfunctions, especially circulatory and respiratory complications. With the rapid development of the world economy, the incidence ofspinal cord injury presents an increasing trend. According to the etiology, pathology, the extent of damage and different parts of the anatomy, spinal cord injury should be divided into different types. Studies have shown that spinal cord injury involves two mechanisms of injury, primary injury and secondary injury. Wherein primary injury occurs passively in a short time after the injury, it is limited and irreversible.The evolution of this disease process is "waterfall" cascades, and its pathogenesis is not entirely clear. Interventionist secondary damage may be formed gradually within a few minutes to several days after the primary injury. The following mechanisms to together participate in the pathological change of Secondary spinal cord injury:microcirculation, free radical damage, excitatory amino acid toxicity, apoptosis and necrosis, nitric oxide mechanism, calcium overload, inflammation, neuropeptides, endothelin, prostaglandins, etc. Data indicate whether primary or secondary damage plays a crucial role in neural tissue functional loss.Due to the complex pathogenesis of this disease, the treatment is very difficult. It will not only bring serious harm to the patient’s own physical and mental, but also cause huge economic burden on the patient’s family and the whole society. Varying degrees of spinal cord injury is caused by multiple directly or indirectly causative factors. In addition to the physical damage, oxidative stress is also involved in the mechanism of central nervous system injury. When our body is subjected to any form of trauma, neurotrophic factors can trigger natural stem cell as an information signal transduction. Spinal cord tissue is rich in lipids, is extremely sensitive to lipid peroxidation.Under physiological conditions, in order to maintain the integrity of the various cells and subcellular structures in human body, endogenous oxidation system includes superoxide dismutase (Superoxide dismutase, SOD) and catalase (Catalase, CAT), etc. can be effectively eliminate free radicals. After spinal cord injury, increased production of free radicals and to remove barriers, spinal cord tissue accumulation of lipid peroxidation products damage the cell membrane structure, fluidity and permeability, while lowering levels of antioxidants and Na+-K+-ATP enzyme system depression, lack of spinal cord tissue blood, oxygen and energy metabolism disorders, intracellular calcium overload, so that mitochondrial electron transport chain uncoupling, but also produce and release large amounts of oxygen free radicals, resulting in the structure and function of nerve cells and myelin damage. Studies suggest that the most important factor that affects treatment and prognosis of spinal cord injury is the difficulty of nerve repair and regeneration, therefore, the main purpose of the treatment of spinal cord injury is to provide a favorable microenvironment for nerve regeneration through a variety of treatments, promoting axonal regeneration of damaged nerve and restoring its function. There is currently no effective cure means for spinal cord injury.The prevention, treatment and rehabilitation of spinal cord injury have become a major issue facing the world.In clinicalpractices, patients with spinal cord injury only inflicted cord decompression and spinal stabilization surgery can not repair damaged spinal cord tissue. With the breakthrough nerve injury molecular pathology, it was discovered neurotrophic factor (Neurotrophicfactors, NTFS) is produced by the body can promote nerve cell survival, growth and differentiation of a class of soluble protein molecules for development and nutrition of the nervous system has an important significance.Glial derived neurotropic factor (GDNF) has been widely distributed in the nervous system, which plays an important role in the process of the development, growth, repair of the nervous system. For a variety of neuronal nutrition, Glial derived neurotropic factor can prevent ischemic cerebrovascular diseases and neurodegenerative diseases. Glial derived neurotropic factor has become one of the hotspots in the field of life sciences.Object:The part of theoretical study was to investigate the awareness of similarities and differences between modern medicine and traditional medicine for spinal cord injuryand their respective characteristics, summarize recent achievements in the pathogenesis of spinal cord injury, dig the current status of neurotrophic factor in the treatment of spinal cord injury, and to provide relevant data to support future research in this field. The major purpose of experimental study was designed to investigate the antioxidant effect of Glial derived neurotropic factor in the rat model of spinal cord injury.Method:PubMed was the main search tools in theory portion. In accordance with strict inclusion and exclusion criteria, published literatures related to neurotrophic factor in the treatment of spinal cord injury were screened for further study. It summarizes the research status in the field of spinal cord injurythrough bibliometrics analysis. A Wistar rat model of spinal cord compression injury was used in the experimental part. A total of sixty healthy adult female Wistar rats were randomized into five groups as follows:(i) G1:sham group, untreated; (ii) G2:operation control group, no treatment after spinal cord injury; (iii) G3:Treatment with 5mg/kg GDNF at 1 hour upon SCI via intranasal; (iv) G4:Treatment with lOmg/kg GDNF at 1 hour upon spinal cord injury via intranasal; and (v) G5:Treatment with 20mg/kg GDNF at 1 hour upon SCI via intranasal. The administration of GDNF took place for five consecutive days for all the groups. Then the assessment of serum total antioxidant status (TOS) and the detection of ROS levels and lipid peroxidation products and protein carbonyl content in spinal cord tissue were performed to evaluation the effect of Glial derived neurotropic factor on oxidative stress in rats with SCI. The determination of antioxidant glutathione (GSH), CAT, SOD, glutathione peroxidase (GPx) activity and glutathione transferase-S (GST) reaction were executed to examine GDNF antioxidant capacity.Result:Bibliometric analysis showed that the research related neurotrophic factor in the treatment of spinal cord injury present an overall upward trend during 1990—2015, and this filed was still a hot topic of current research. As of 2015, the most original articles about neurotrophic factor in the treatment of spinal cord injury were published by the United States, and then followed by China, Japan, Canada, and Sweden. There were nine neuroscience-related professional journals (90%,9/10) in the top 10 of the total amount of published literature journalranking, only the impact factor of "journal of neuroscience" was more than five. The top 10 hot spots associated words were nerve growth factor (Nerve Growth Factors, NGF), functional recovery (Recovery of Function), neurotrophin receptor binding (neurotrophin receptor binding), nerve regeneration (Nerve Regeneration), Stem Cells (Stem Cells), neuronal plasticity (neuronal plasticity), neurotrophin-3 (Neurotrophin 3, NT-3), BDNF, trkB receptor (receptor, trkB), glutathione regulate potassium efflux system protein kefB (glutathione-regulated potassium-efflux system protein kefB). Experimental study noted that GDNF had reduced oxidative damages and increased the levels of anti-oxidants in dose-dependent manner (p<0.05). Though treatment with 10mg/mL and 20mg/mL showed significant changes as compared to control group, these treatment modalities remained insignificant among each other.Conclusion:We demonstrated thatGlial derived neurotropic factor exerted a neuro-protective effect on Central nervous system by inducing anti-oxidants and reducing the levels of oxidative stress in spinal cord injuryinduced rat models. |
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