Critical Role of p38 in Spinal Cord Injury by Regulating Inflammation and Apoptosis in a Rat Model.
- 作者列表："Zhang HW","Ding JD","Zhang ZS","Zhao SS","Duan KY","Zhu BQ","Zhao WF","Chai ZT","Liu XW
STUDY DESIGN:To evaluate the effect of p38 pathway on spinal cord injury (SCI), a rat model of SCI was performed. OBJECTIVE:We determined the effect of p38 on SCI and SCI related inflammation, apoptosis, and autophagy. SUMMARY OF BACKGROUND DATA:SCI is a severe clinical problem worldwide. It is difficult to prevent cell necroptosis and promote the survival of residual neurons after SCI. p38, a class of mitogen-activated protein kinases, its effect on SCI and SCI related inflammation, apoptosis, and autophagy have not been studied very well. METHODS:The rats were randomly divided into the following four groups: the sham-operated (sham) group, the SCI group, the SCI + vehicle group, and the SCI + SB203580 (10 mg/kg) group. The p38 inhibitor SB203580 was administered by oral (10 mg/kg/d) gavage once per day for 14 days. Neurological recovery was assessed using the Basso, Beattie, and Bresnahan locomotion rating scale. Apoptosis, autophagy, and inflammation related proteins were measured by enzyme-linked immunosorbent assay kits or western blotting. RESULTS:Our results showed that p38 was upregulated after SCI from day 3, which was paralleled with the levels of its proteins ATF-2, suggesting an increase in p38 activity. Our results showed administration of SB203580 attenuated histopathology and promoted locomotion recovery in rats after SCI. SB203580 administration significantly inhibited inflammatory cytokines levels as well as the inflammation signaling pathway. SB203580 administration also modulated the apoptosis and autophagy signaling pathway. CONCLUSION:Our findings suggest that p38 inhibitor SB203580 treatment alleviates secondary SCI by inhibiting inflammation and apoptosis, thereby promoting neurological and locomoter functional recovery, thus suggest the important role of p38 in neuronal protection after SCI. LEVEL OF EVIDENCE:N/A.
研究设计: 采用大鼠脊髓损伤模型，评价 p38 通路在脊髓损伤中的作用。 目的: 我们确定 p38 对 SCI 和 SCI 相关的炎症、凋亡和自噬的影响。 背景资料摘要: SCI 是一个世界性的严重临床问题。很难预防细胞坏死性凋亡，促进 SCI 后残余神经元的存活。p38 是一类丝裂原活化蛋白激酶，其对 SCI 和 SCI 相关炎症、细胞凋亡和自噬的影响尚未得到很好的研究。 方法: 将大鼠随机分为假手术组、 SCI 组、 SCI + vehicle 组、 SCI + SB203580 (10 mg/kg) 组。P38 抑制剂 SB203580 口服 (10 mg/kg/d) 灌胃，1 次/d，共 14 天。使用 Basso 、 Beattie 和 Bresnahan 运动评定量表评估神经功能恢复。通过酶联免疫吸附测定试剂盒或 免疫印迹测定细胞凋亡、自噬和炎症相关蛋白。 结果: 我们的结果表明，从第 3 天开始，SCI 后 p38 上调，与其 ATF-2 蛋白水平平行，表明 p38 活性增加。我们的结果显示给予 SB203580 可减弱 SCI 后大鼠的组织病理学和促进运动恢复。SB203580 给药可显著抑制炎症细胞因子水平以及炎症信号通路。SB203580 给药也调节了细胞凋亡和自噬信号通路。 结论: p38 抑制剂 SB203580 通过抑制炎症和细胞凋亡，缓解继发性 SCI，从而促进神经和运动功能恢复，从而提示 p38 在 SCI 后神经元保护中的重要作用。 证据级别: N/A。
METHODS:Objective To clarify the existence of monophasic neuromyelitis optica spectrum disorders (NMOSD) and to identify predictive factors of long-term relapse-free form. Methods We retrospectively analyzed 289 Chinese patients with NMOSD. Selected subjects were divided into three groups based on the time interval between disease onset and the first relapse, if any. Clinical and imaging data were acquired from each patient’s medical record and evaluated as predictive factors for NMOSD. Results In total, none of the participating patients exhibited a monophasic form of NMOSD. Rather, 241 patients were selected for relapse tendency analysis; 143 (59.3%) patients relapsed within the first year, 66 (27.4%) during 1–5 years, and 32 (13.3%) beyond 5 years. Such onset symptoms as optic neuritis (ON) and non-longitudinally extensive transverse myelitis (LETM) were independent prognostic factors for a prolonged remission interval.
METHODS::Neuromyelitis optica spectrum disorders (NMOSD) are an inflammation of the central nervous system associated with autoantibodies to aquaporin-4. We have undertaken a clinic-based survey of NMOSD in the Australia and New Zealand populations with the aim of characterising the clinical features and establishing the value of recently revised diagnostic criteria. Cases of possible NMOSD and age and sex-matched controls with multiple sclerosis (MS) were referred from centres across Australia and New Zealand. Cases were classified as NMOSD if they met the 2015 IPND criteria and remained as suspected NMOSD if they did not. Clinical and paraclinical data were compared across the three groups. NMOSD was confirmed in 75 cases and 89 had suspected NMOSD. There were 101 controls with MS. Age at onset, relapse rates and EDSS scores were significantly higher in NMOSD than in MS. Lesions and symptoms referable to the optic nerve were more common in NMOSD whereas brainstem, cerebellar and cerebral lesions were more common in MS. Longitudinally extensive spinal cord lesions were seen in 48/71 (68%) of cases with NMOSD. Elevations of CSF, white cell count and protein were more common in NMOSD. We have confirmed a clinical pattern of NMOSD that has been seen in several geographical regions. We have demonstrated the clinical utility of the current diagnostic criteria. Distinct patterns of disease are evident in NMOSD and MS, but there remains a large number of patients with NMOSD-like features who do not meet the current diagnostic criteria for NMOSD and remain a diagnostic challenge.
METHODS:Spinal cord injury (SCI) is a traumatic lesion that causes disability with temporary or permanent sensory and/or motor deficits. The pharmacological approach still in use for the treatment of SCI involves the employment of corticosteroid drugs. However, SCI remains a very complex disorder that needs future studies to find effective pharmacological treatments. SCI actives a strong inflammatory response that induces a loss of neurons followed by a cascade of events that lead to further spinal cord damage. Many experimental studies demonstrate the therapeutic effect of stem cells in SCI due to their capacity to differentiate into neuronal cells and by releasing neurotrophic factors. Therefore, they appear to be a valid strategy to use in the field of regenerative medicine. The purpose of this paper is to provide an overview of clinical trials, recorded in clinical trial.gov during 2005−2019, aimed to evaluate the use of stem cell-based therapy in SCI. The results available thus far show the safety and efficacy of stem cell therapy in patients with SCI. However, future trials are needed to investigate the safety and efficacy of stem cell transplantation.