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Pathophysiology of spinal cord injury

Sai-Nan Wang, Xue-Yan Guo, Jie Tang, Shu-Qin Ding, Lin Shen, Rui Wang, Shan-Feng Ma, Jian-Guo Hu, He-Zuo Lü
In traumatic brain injury, absent in melanoma 2 (AIM2) has been demonstrated to be involved in pyroptotic neuronal cell death. Although the pathophysiological mechanism of spinal cord injury is similar to that of brain injury, the expression and cellular localization of AIM2 after spinal cord injury is still not very clear. In the present study, we used a rat model of T9 spinal cord contusive injury, produced using the weight drop method. The rats were randomly divided into 1-hour, 6-hour, 1-day, 3-day and 6-day (post-injury time points) groups...
March 2019: Neural Regeneration Research
Wei-Kang Xue, Wei-Jiang Zhao, Xiang-He Meng, Hui-Fan Shen, Pei-Zhi Huang
Accumulated evidence has recently demonstrated that spinal cord injury (SCI) can lead to chronic damage in a wide range of brain regions. Neuregulin 1 (Nrg1) signaling has been broadly recognized as an important mechanism contributing to neural differentiation and regeneration. We here studied the effect of SCI on Nrg1 signaling in prefrontal cortex (PFC) and hippocampus (HIP) in a mouse model. As was indicated by the increased levels of GFAP and Iba-1, our results demonstrated that SCI significantly induced activation of astrocytes and microglial cells in both PFC and HIP...
December 7, 2018: Brain Research Bulletin
Kazue Hashimoto-Torii, Masanori Sasaki, Yu-Wen Chang, Hye Hwang, Stephen G Waxman, Jeffery D Kocsis, Pasko Rakic, Masaaki Torii
Spinal cord and peripheral nerve injury results in extensive damage to the locally injured cells as well as distant cells that are functionally connected to them. Both primary and secondary damage can cause a broad range of clinical abnormalities, including neuropathic pain and cognitive and memory dysfunction. However, the mechanisms underlying these abnormalities remain unclear, awaiting new methods to identify affected cells to enable examination of their molecular, cellular and physiological characteristics...
December 2018: IBRO Reports
Yonglin Chen, Dekun Yin, Bingbing Fan, Xiang Zhu, Qiuping Chen, Yao Li, Shunxing Zhu, Rongxiang Lu, Zhongling Xu
Inflammatory cytokines and chemokines play essential roles in the occurrence and persistence of neuropathic pain (NP). Chronic constriction injury (CCI) enhances the activation of p-ERK, which is involved in neuropathic pain. Although the chemokine CXCL10 and its receptor CXCR3 are implicated in the pathophysiology of itch, it is largely unexplored for neuropathic pain. In this study, we determined the role of the CXCL10-CXCR3 axis in NP using a well-established CCI model. CCI significantly induced mechanical allodynia and thermal hyperalgesia...
November 15, 2018: Neuroscience Letters
Tianyi Wang, Bo Li, Xin Yuan, Libin Cui, Zhijie Wang, Yanjun Zhang, Mei Yu, Yucai Xiu, Zheng Zhang, Wenhua Li, Fengyan Wang, Xiaoling Guo, Xiangyang Zhao, Xueming Chen
Spinal cord injury (SCI) causes sensory dysfunctions such as paresthesia, dysesthesia, and chronic neuropathic pain. MiR-20a facilitates the axonal outgrowth of the cortical neurons. However, the role of miR-20a in the axonal outgrowth of primary sensory neurons and spinal cord dorsal column lesion (SDCL) is yet unknown. Therefore, the role of miR-20a post-SDCL was investigated in rat. The NF-200 immunofluorescence staining was applied to observe whether axonal outgrowth of dorsal root ganglion (DRG) neurons could be altered by miR-20a or PDZ-RhoGEF modulation in vitro...
November 13, 2018: Cellular and Molecular Neurobiology
Johannes Walter, Klaus Zweckberger
The term "traumatic injuries of the central nervous system" (CNS) refers to both traumatic brain injury (TBI) as well as traumatic spinal cord injury (SCI). Both types of injuries substantially contribute to morbidity and mortality in developed as well as developing countries. The underlying pathophysiological processes are very complex and despite extensive research efforts they are still not completely understood. Therefore, traumatic injuries to the CNS pose special challenges for preclinical and clinical management...
October 2018: Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie: AINS
Azim Patar, Peter Dockery, Linda Howard, Siobhan S McMahon
Spinal cord injury (SCI) is a devastating disorder that has a poor prognosis of recovery. Animal models of SCI are useful to understand the pathophysiology of SCI and the potential use of therapeutic strategies for human SCI. Ex vivo models of central nervous system (CNS) trauma, particularly mechanical trauma, have become important tools to complement in vivo models of injury in order to reproduce the sequelae of human CNS injury. Ex vivo organotypic slice cultures (OSCs) provide a reliable model platform for the study of cell dynamics and therapeutic intervention following SCI...
November 11, 2018: Journal of Anatomy
Jusal Quanico, Lena Hauberg-Lotte, Stephanie Devaux, Zahra Laouby, Celine Meriaux, Antonella Raffo-Romero, Melanie Rose, Leia Westerheide, Jost Vehmeyer, Franck Rodet, Peter Maass, Dasa Cizkova, Norbert Zilka, Veronika Cubinkova, Isabelle Fournier, Michel Salzet
We report, for the first time, the detection and specific localization of long-chain acylcarnitines (LC ACs) along the lesion margins in an experimental model of spinal cord injury (SCI) using 3D mass spectrometry imaging (MSI). Acylcarnitines palmitoylcarnitine (AC(16:0)), palmitoleoylcarnitine (AC(16:1)), elaidic carnitine (AC(18:1)) and tetradecanoylcarnitine (AC(14:1)) were detected as early as 3 days post injury, and were present along the lesion margins 7 and 10 days after SCI induced by balloon compression technique in the rat...
October 31, 2018: Scientific Reports
Yan Zhang, Chao Sun, Chenxi Zhao, Jian Hao, Yiling Zhang, Baoyou Fan, Bo Li, Huiquan Duan, Chang Liu, Xiaohong Kong, Ping Wu, Xue Yao, Shiqing Feng
Cell death is a key issue in spinal cord secondary injury. Ferroptosis is recently discovered as an iron-dependent type of cell death that is distinct from other forms of cell death pathways such as apoptosis and necrosis. This research is aimed to investigate the role of ferroptosis in spinal cord injury (SCI) pathophysiology, and to explore the effectiveness of ferroptosis inhibitor on SCI. We examined the ferroptosis markers and the factors in a rat contusion SCI model. Seen from transmission electron microscopy (TEM) following SCI, mitochondria showed ferroptotic characteristic changes...
October 20, 2018: Brain Research
Sohaib Z Hashmi, Angelo Marra, Louis G Jenis, Alpesh A Patel
Central cord syndrome (CCS) represents a clinical phenomenon characterized by disproportionately greater motor impairment of the upper than of the lower extremities, bladder dysfunction. CSS is the most common form of incomplete traumatic spinal cord injury. The initial description of CSS was reported in 1887 secondary to cervical spinal trauma. However, recent literature describes a heterogenous injury patterns including high-energy and low-energy mechanisms and bimodal patient age distributions. Pathophysiology of clinical symptoms and neurological deficits often is affected by preexisting cervical spondylosis...
October 22, 2018: Clinical Spine Surgery
Shijie Zhang, Hui Liu, Qing Xu, Fei Huang, Ranran Xu, Qingquan Liu, Yongman Lv
Acute kidney injury (AKI) is a common kidney disorder which is associated with a high risk of mortality. Extensive evidence revealed the participation of renal afferent sensory nerves in the pathophysiology of renal ischemia reperfusion (IR) injury, however the role of these nerves in renal IR injury is controversial and remains to be further explored. Here, we report that capsaicin sensitive sensory nerves and neuropeptides prevented renal damage in AKI induced by IR injury. The sensory afferent degeneration model was established by injecting 50 mg/kg of capsaicin to male neonatal rats and verified by the tail flick test and reduced sensory neuropeptide of substance P and calcitonin gene related peptide in spinal cord, dorsal root ganglion and kidney after 12 weeks...
October 17, 2018: Biochemical and Biophysical Research Communications
Andrea M Halsey, Alex C Conner, Roslyn M Bill, Ann Logan, Zubair Ahmed
After injury to the spinal cord, edema contributes to the underlying detrimental pathophysiological outcomes that lead to worsening of function. Several related membrane proteins called aquaporins (AQPs) regulate water movement in fluid transporting tissues including the spinal cord. Within the cord, AQP1, 4 and 9 contribute to spinal cord injury (SCI)-induced edema. AQP1, 4 and 9 are expressed in a variety of cells including astrocytes, neurons, ependymal cells, and endothelial cells. This review discusses some of the recent findings of the involvement of AQP in SCI and highlights the need for further study of these proteins to develop effective therapies to counteract the negative effects of SCI-induced edema...
October 18, 2018: Cells
Luyao Xu, Benson O A Botchway, Songou Zhang, Jingying Zhou, Xuehong Liu
Spinal cord injury (SCI) can have a significant impact on an individual's life. Herein, we discuss how resveratrol improves SCI by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Evidences show resveratrol suppresses NF-κB signaling pathway to exert its beneficial effects on various diseases. NF-κB signaling pathway plays a significant role in the pathophysiological mechanisms of SCI including increase in inflammation, augmentation of damage caused by free radicals and lipid peroxidation as well as facilitation of apoptosis and axonal demyelination...
2018: Frontiers in Neuroscience
Tong Niu, Liuzhong Jin, Shizhen Niu, Cunqi Gong, Hui Wang
BACKGROUND/AIMS: Currently, scientists attempt to improve outcome of spinal cord injury (SCI) via reducing secondary injury during SCI. Oxidative stress is critical for pathophysiology of secondary damage, thus we mainly focused on the anti-oxidant effects of Lycium barbarum polysaccharides (LBPs) on PC-12 and SH-SY5Y cells as well as the underlying mechanisms. METHODS: Oxidative stress was induced by H2O2 stimulation. Effects of LBPs on cell viability, apoptosis, and expression of proteins associated with apoptosis and autophagy in H2O2-induced cells were assessed by CCK-8 assay, flow cytometry assay and Western blot analysis, respectively...
2018: Cellular Physiology and Biochemistry
Karl Balsara, Andrew Jea, Jeffrey S Raskin
Spasticity is a hypertonic segmental reflex pathway caused by a central nervous system injury. Spasticity of the upper extremity causes loss of function, joint contracture, pain, and poor cosmesis. Treatment aims to reduce or change the pathophysiology underlying the hyperactive reflex from dorsal sensory rootlets through the intrinsic machinery of the spinal cord to the neuromuscular junction. There are many treatments for upper extremity spasticity including oral medication, physiotherapy, intrathecal baclofen, and lesional or neuromodulatory surgical approaches...
November 2018: Hand Clinics
Michael S Gart, Joshua M Adkinson
Spasticity is a movement disorder characterized by a velocity-dependent increase in muscle tone and a hyperexcitable stretch reflex. Common causes of spasticity include cerebral palsy, spinal cord injury, and stroke. Surgical treatment plans for spasticity must be highly individualized and based on the characteristics of patients and the spasticity in order to maximize functional gains. Candidates for surgery must be carefully selected. In this article, the authors review the pathophysiology of spasticity and discuss general considerations for surgical management with an emphasis on patient factors and spasticity characteristics...
November 2018: Hand Clinics
Francisco J Angulo-Parker, Joshua M Adkinson
Spasticity is a motor disorder that manifests as a component of the upper motor neuron syndrome. It is associated with paralysis and can cause significant disability. The most common causes leading to spasticity include stroke, traumatic brain injury, multiple sclerosis, spinal cord injury, and cerebral palsy. This article discusses the pathophysiology and clinical findings associated with each of the most common etiologies of upper extremity spasticity.
November 2018: Hand Clinics
Jordan W Squair, Seth Tigchelaar, Kyung-Mee Moon, Jie Liu, Wolfram Tetzlaff, Brian K Kwon, Andrei V Krassioukov, Christopher R West, Leonard J Foster, Michael A Skinnider
Spinal cord injury (SCI) is a devastating neurological condition for which there are currently no effective treatment options to restore function. A major obstacle to the development of new therapies is our fragmentary understanding of the coordinated pathophysiological processes triggered by damage to the human spinal cord. Here, we describe a systems biology approach to integrate decades of small-scale experiments with unbiased, genome-wide gene expression from the human spinal cord, revealing a gene regulatory network signature of the pathophysiological response to SCI...
October 2, 2018: ELife
Yuan Zhou, Ning Li, Lin Zhu, Yixing Lin, Huilin Cheng
Background: Spinal cord injury (SCI) has imposed a great impact on the quality of life of patients due to its relatively young age of onset. The pathophysiology of SCI has been proven to be complicated. Microglia plays an important role in neuroinflammation and second injuries after SCI. Different environment and other factors may determine the microglial activation profile and what role they play. However, neither accurate time-course profiles of microglial activation nor influence factors have been demonstrated in varied SCI models...
2018: Neuropsychiatric Disease and Treatment
Maria Bertuzzi, Weipang Chang, Konstantinos Ampatzis
A particularly essential determinant of a neuron's functionality is its neurotransmitter phenotype. While the prevailing view is that neurotransmitter phenotypes are fixed and determined early during development, a growing body of evidence suggests that neurons retain the ability to switch between different neurotransmitters. However, such changes are considered unlikely in motoneurons due to their crucial functional role in animals' behavior. Here we describe the expression and dynamics of glutamatergic neurotransmission in the adult zebrafish spinal motoneuron circuit assembly...
October 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
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