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Ferroptosis:a critical player and potential therapeutic target in traumatic brain injury and spinal cord injury

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Neural Regeneration Research 2023年第3期18卷 506-512页

作者： Qing-Sheng Li Yan-Jie Jia Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan ProvinceChina

Ferroptosis,a new non-necrotizing programmed cell death(PCD),is driven by iron-dependent phospholipid *** plays a key role in secondary traumatic brain injury and secondary spinal cord injury and is closely related to inflammation,immunity,and chronic *** inhibitors against ferroptosis effectively improve iron homeostasis,lipid metabolism,redox stabilization,neuronal remodeling,and functional recovery after *** this review,we elaborate on the latest molecular mechanisms of ferroptosis,emphasize its role in secondary central nervous trauma,and update the medicines used to suppress ferroptosis following injuries.

关键词： ferroptosis immune response inflammation iron homeostasis lipid metabolism medicine programmed cell death spinal cord injury traumatic brain injury

Three-dimensional bioprinting sodium alginate/gelatin scaffold combined with neural stem cells and oligodendrocytes markedly promoting nerve regeneration after spinal cord injury

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Regenerative Biomaterials 2022年第1期9卷 522-532页

作者： Shuo Liu Hui Yang Dong Chen Yuanyuan Xie ChenXu Tai Liudi Wang Peng Wang Bin Wang Clinical Stem Cell Center Nanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210000Jiangsu ProvinceChina State Key Laboratory of Pharmaceutical Biotechnology Department of Sports Medicine and Adult Reconstructive SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210000Jiangsu ProvinceChina

Accumulating research has indicated that the transplantation of combined stem cells and scaffolds is an effective method for spinal cord injury(SCI).The development of three-dimensional(3D)bioprinting technology can make the 3D scaffolds combined with cells more accurate and effective for SCI ***,unmyelinated newborn nerve fibers have no nerve signaling conduction,hampering recovery of motor *** this study,we designed and printed a type of sodium alginate/gelatin scaffold loaded with neural stem cells and oligodendrocytes,which were involved in the formation of the myelin sheaths of neural cell *** order to observe the effectiveness of this 3D bioprinting scaffold,we transplanted it into the completely transected rat spinal cord,and then immunofluorescence staining,hematoxylin–eosin staining and behavioral assessment were *** results showed that this 3D bioprinting scaffold markedly improved the hindlimb motor function and promoted nerve *** findings suggested that this novel 3D bioprinting scaffold was a good carrier for cells transplantation,thereby enhancing spinal cord repair following injury.

关键词： three-dimensional bioprinting neural stem cell oligodendrocytes spinal cord injury

Combination of methylprednisolone and rosiglitazone promotes recovery of neurological function after spinal cord injury

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Neural Regeneration Research 2016年第10期11卷 1678-1684页

作者： Xi-gong Li Xiang-jin Lin Jun-hua Du San-zhong Xu Xian-feng Lou Zhong Chen Department of Orthopedic Surgery First Affiliated Hospital School of Medicine Zhejiang University

Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-y in the spinal cord. Methylprednisolone and rosiglitazone have been clinically used during the early stages of secondary spinal cord injury. Because of the complexity and diversity of the inflammatory process after spinal cord injury, a single drug cannot completely inhibit inflammation. Therefore, we assumed that a combination of methylprednisolone and rosiglitazone might promote recovery of neurological function after secondary spinal cord injury. In this study, rats were intraperitoneally rejected with methylprednisolone （30 mg/kg） and rosiglitazone （2 mg/kg） at 1 hour after injury, and methylprednisolone （15 mg/kg） at 24 and 48 hours after injury. Rosiglitazone was then administered once every 12 hours for 7 consecutive days. Our results demonstrated that a combined treatment with methylprednisolone and rosiglitazone had a more pronounced effect on attenuation of inflammation and cell apoptosis, as well as increased functional recovery, compared with either single treatment alone, indicating that a combination better pro- moted recovery of neurological function after injury.

关键词： nerve regeneration spinal cord injury methylprednisotone rosiglitazone inflammation drug therapy anti-inflammatory agents functional recovery neural regeneration

Human umbilical cord blood stem cell transplantation for the treatment of chronic spinal cord injury Electrophysiological changes and long-term efficacy

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Neural Regeneration Research 2013年第5期8卷 397-403页

作者： Liqing Yao Chuan He Ying Zhao Jirong Wang Mei Tang Jun Li Ying Wu Lijuan Ao Xiang Hu Department of Rehabilitation Second Affiliated Hospital of Kunming Medical University Shenzhen Beike Cell Engineering Research Institute

Stem cell transplantation can promote functional restoration following acute spinal cord injury （injury time 〈 3 months）, but the safety and long-term efficacy of this treatment need further exploration. In this study, 25 patients with traumatic spinal cord injury （injury time 〉 6 months） were treated with human umbilical cord blood stem cells via intravenous and intrathecal injection. The follow-up period was 12 months after transplantation. Results found that autonomic nerve functions were restored and the latent period of somatosensory evoked potentials was reduced. There were no severe adverse reactions in patients following stem cell transplantation. These experimental findings suggest that the transplantation of human umbilical cord blood stem cells is a safe and effective treatment for patients with traumatic spinal cord injury

关键词： neural regeneration spinal cord injury human umbilical cord blood stem cells transplantation paraplegia American spinal cord injury Association score neurological function secretion somatosensory evoked potentials spasm safety photographs-containing paper neurogeneration

Transplantation of human telomerase reverse transcriptase gene-transfected Schwann cells for repairing spinal cord injury

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Neural Regeneration Research 2015年第12期10卷 2040-2047页

作者： Shu-quan Zhang Min-fei Wu Jia-bei Liu Ye Li Qing-san Zhu Rui Gu Department of Orthopedics Tianjin Nankai Hospital Department of Spine Surgery Orthopedic HospitalSecond HospitalClinical HospitalJilin University Department of Orthopedics China-Japan Union HospitalJilin University

Transfection of the human telomerase reverse transcriptase（h TERT）gene has been shown to increase cell proliferation and enhance tissue *** the present study,h TERT was transfected into rat Schwann cells.A rat model of acute spinal cord injury was established by the modified free-falling *** PLXSN was injected at the site of spinal cord injury as a vector to mediate h TERT gene-transfected Schwann cells（1×10^（10）/L;10μL）or Schwann cells（1×10^（10）/L;10μL）without h TERT gene *** 1 and 4 weeks after model establishment,motor function of the lower limb improved in the h TERT-transfected group compared with the group with non-transfected Schwann *** deoxynucleotidyl transferase-mediated d UTP nick-end labeling and reverse transcription-polymerase chain reaction results revealed that the number of apoptotic cells,and gene expression of aquaporin 4/9 and matrix metalloproteinase 9/2decreased at the site of injury in both groups;however,the effect improved in the h TERT-transfected group compared with the Schwann cells without h TERT transfection *** and eosin staining,PKH26 fluorescent labeling,and electrophysiological testing demonstrated that compared with the non-transfected group,spinal cord cavity and motor and sensory evoked potential latencies were reduced,while the number of PKH26-positive cells and the motor and sensory evoked potential amplitude increased at the site of injury in the h TERT-transfected *** findings suggest that transplantation of h TERT gene-transfected Schwann cells repairs the structure and function of the injured spinal cord.

关键词： nerve regeneration spinal cord injury Schwann cells transplantation motor function telomerase reverse transcriptase proliferation modification cells neural regeneration

Protein post-translational modifications after spinal cord injury

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Neural Regeneration Research 2021年第10期16卷 1935-1943页

作者： Shuang Zhu Bing-Sheng Yang Si-Jing Li Ge Tong Jian-Ye Tan Guo-Feng Wu Lin Li Guo-Li Chen Qian Chen Li-Jun Lin Department of Joint and Orthopedics Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Medical Ultrasonics Guangdong Province Key Laboratory of Hepatology ResearchThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedics Affiliated Hospital of Putian UniversityPutianFujian ProvinceChina Cell and Molecular Biology Laboratory Department of OrthopaedicsAlpert Medical School of Brown University/Rhode Island HospitalProvidenceRIUSA

Deficits in intrinsic neuronal capacities in the spinal cord,a lack of growth support,and suppression of axonal outgrowth by inhibitory molecules mean that spinal cord injury almost always has devastating *** such,one of the primary targets for the treatment of spinal cord injury is to develop strategies to antagonize extrinsic or intrinsic axonal growth-inhibitory factors or enhance the factors that support axonal *** these factors,a series of individual protein level disorders have been identified during the generation of axons following spinal cord ***,an increasing number of studies have indicated that post-translational modifications of these proteins have important implications for axonal *** researchers have discovered a variety of post-translational modifications after spinal cord injury,such as tyrosination,acetylation,and *** this review,we reviewed the post-translational modifications for axonal growth,functional recovery,and neuropathic pain after spinal cord injury,a better understanding of which may elucidate the dynamic change of spinal cord injury-related molecules and facilitate the development of a new therapeutic strategy for spinal cord injury.

关键词： extracellular matrix function impairment glial scar nerve regeneration neuropathic pain post-translational modification spinal cord injury therapeutic target

Differences in neuroplasticity after spinal cord injury in varying animal models and humans

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Neural Regeneration Research 2019年第1期14卷 7-19页

作者： Mallory E.Filipp Benjamin J.Travis Stefanie S.Henry Emma C.Idzikowski Sarah A.Magnuson Megan YF Loh Daniel J.Hellenbrand Amgad S.Hanna Department of Neurological Surgery University of Wisconsin

Rats have been the primary model to study the process and underlying mechanisms of recovery after spinal cord injury. Two weeks after a severe spinal cord contusion, rats can regain weight-bearing abilities without therapeutic interventions, as assessed by the Basso, Beattie and Bresnahan locomotor scale. However, many human patients suffer from permanent loss of motor function following spinal cord injury. While rats are the most understood animal model, major differences in sensorimotor pathways between quadrupeds and bipeds need to be considered. Understanding the major differences between the sensorimotor pathways of rats, non-human primates, and humans is a start to improving targets for treatments of human spinal cord injury. This review will discuss the neuroplasticity of the brain and spinal cord after spinal cord injury in rats, non-human primates, and humans. A brief overview of emerging interventions to induce plasticity in humans with spinal cord injury will also be discussed.

关键词： recovery regeneration spinal cord injury plasticity axons animal studies locomotor training functional recovery

Neurophysiological, histological, and behavioral characterization of animal models of distraction spinal cord injury: a systematic review

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Neural Regeneration Research 2024年第3期19卷 563-570页

作者： Bo Han Weishi Liang Yong Hai Duan Sun Hongtao Ding Yihan Yang Peng Yin Department of Orthopedics Beijing Chao-Yang HospitalCapital Medical UniversityBeijingChina

Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal *** the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and *** few studies have been published on the specific characteristics of distraction spinal cord *** this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this *** addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord *** provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.

关键词： animal models behavior distraction heterogeneity histology mechanism neurophysiology spinal cord injury systematic review tension

Potential role of hippocampal neurogenesis in spinal cord injury induced post-trauma depression

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Neural Regeneration Research 2024年第10期19卷 2144-2156页

作者： Ying Ma Yue Qiao Xiang Gao spinal cord and Brain injury Research Group Stark Neuroscience Research InstituteIndianapolisINUSA Department of Neurological Surgery Indiana University School of MedicineIndianapolisINUSA Department of Neurology Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

It has been reported both in clinic and rodent models that beyond spinal cord injury directly induced symptoms, such as paralysis, neuropathic pain, bladder/bowel dysfunction, and loss of sexual function, there are a variety of secondary complications, including memory loss, cognitive decline, depression, and Alzheimer's disease. The largescale longitudinal population-based studies indicate that post-trauma depression is highly prevalent in spinal cord injury patients. Yet, few basic studies have been conducted to address the potential molecular mechanisms. One of possible factors underlying the depression is the reduction of adult hippocampal neurogenesis which may come from less physical activity, social isolation, chronic pain, and elevated neuroinflammation after spinal cord injury. However, there is no clear consensus yet. In this review, we will first summarize the alteration of hippocampal neurogenesis post-spinal cord injury. Then, we will discuss possible mechanisms underlie this important spinal cord injury consequence. Finally, we will outline the potential therapeutic options aimed at enhancing hippocampal neurogenesis to ameliorate depression.

关键词： antidepressants chronic pain depression exercise hippocampal neurogenesis inflammation inhibition neuroinflammation physical activity deficits social isolation spinal cord injury