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Pathophysiology of spinal cord injury

Marc Parisien, Alexander Samoshkin, Shannon N Tansley, Marjo H Piltonen, Loren J Martin, Nehme El-Hachem, Concetta Dagostino, Massimo Allegri, Jeffrey S Mogil, Arkady Khoutorsky, Luda Diatchenko
Chronic pain is a debilitating and poorly treated condition whose underlying mechanisms are poorly understood. Nerve injury and inflammation cause alterations in gene expression in tissues associated with pain processing, supporting molecular and cellular mechanisms that maintain painful states. However, it is not known whether transcriptome changes can be used to reconstruct a molecular pathophysiology of pain. In the current study, we identify molecular pathways contributing to chronic pain states through the analysis of global changes in the transcriptome of dorsal root ganglia, spinal cord, brain, and blood in mouse assays of nerve injury- and inflammation-induced pain...
January 3, 2019: Pain
Ahmed A Albayar, Abigail Roche, Przemyslaw Swiatkowski, Sarah Antar, Nouran Ouda, Eman Emara, Douglas H Smith, Ali K Ozturk, Basem I Awad
Spinal Cord Injury (SCI) is a major challenge in Neurotrauma research. Complex pathophysiological processes take place immediately after the injury and later on as the chronic injury develops. Moreover, SCI is usually accompanied by traumatic injuries because the most common modality of injury is road traffic accidents and falls. Patients develop significant permanent neurological deficits that depend on the extent and the location of the injury itself and in time they develop further neurological and body changes that may risk their mere survival...
2019: Frontiers in Neurology
Siavash Piran, Sam Schulman
Patients with acute spinal cord injury (SCI) have the highest risk of venous thromboembolism (VTE) among hospitalized patients. The incidence of total deep vein thrombosis ranges from 50 to 100% in untreated patients and pulmonary embolism is the third most common cause of mortality in these patients. The pathophysiology of the increased risk of VTE is explained by venous stasis after injury, endothelial vessel wall injury from surgery, and a hypercoagulable state associated with trauma. The current thromboprophylaxis options are limited, with low-molecular-weight heparin (LMWH) being the current standard of care...
February 11, 2019: Seminars in Thrombosis and Hemostasis
Zahra Hassannejad, Aida Shakouri-Motlagh, Mona Mokhatab, Shayan Abdollah Zadegan, Mahdi Sharif-Alhoseini, Farhad Shokraneh, Vafa Rahimi-Movaghar
Extensive oligodendrocyte death after acute traumatic spinal cord injuries (TSCI) leads to axon demyelination and subsequently may leave axons vulnerable to degeneration. Despite the present evidence showing spontaneous remyelination after TSCI the cellular origin of new myelin and the time course of the axon ensheatment/remyelination remained controversial issue. In this systematic review the trend of oligodendrocyte death after injury as well as the extent and the cellular origin of oligodendrogliogenesis were comprehensively evaluated...
January 24, 2019: Neuroscience
Miriam Aceves, Mabel N Terminel, Andre Okoreeh, Alejandro R Aceves, Yan Ming Gong, Alan Polanco, Farida Sohrabji, Michelle A Hook
Opioids are among the most effective and widely prescribed medications for the treatment of pain following spinal cord injury (SCI). Spinally-injured patients receive opioids within hours of arrival at the emergency room, and prolonged opioid regimens are often employed for the management of post-SCI chronic pain. However, previous studies in our laboratory suggest that the effects of opioids such as morphine may be altered in the pathophysiological context of neurotrauma. Specifically, we have shown that morphine administration in a rodent model of SCI increases mortality and tissue loss at the injury site, and decreases recovery of motor and sensory function, and overall health, even weeks after treatment...
January 23, 2019: Brain, Behavior, and Immunity
Zhi-Bin Zhou, Di Du, Kai-Zhe Chen, Lianfu Deng, Yu-Long Niu, Lei Zhu
Recent studies have indicated that circular RNAs (circRNAs) are involved in a variety of human diseases. However, the roles of circRNAs in traumatic spinal cord injury (SCI) remain unknown. Here, we performed RNA-seq to analyze the circRNA expression profile in rat spinal cord after SCI and investigate the relevant mechanisms. In all, 150 circRNAs were significantly differentially expressed in rat spinal cord after SCI by a fold-change ≥2 and p-value ≤0.05. Among these, 99 circRNAs were up-regulated, while 51 were down-regulated...
January 25, 2019: Journal of Neurotrauma
TaeHee Kim, Bharath Chelluboina, Anil K Chokkalla, Raghu Vemuganti
Despite the immeasurable burden on patients and families, no effective therapies to protect the CNS after an acute injury are available yet. Furthermore, the underlying mechanisms that promote neuronal death and functional deficits after injury remain to be poorly understood. The prevalence, age of onset, pathophysiology, and symptomatology of many CNS insults differ significantly between males and females. In the case of stroke, younger males tend to show a higher risk than younger females, while this trend reverses with age...
January 14, 2019: Neurochemistry International
Kazuya Yokota, Kensuke Kubota, Kazu Kobayakawa, Takeyuki Saito, Masamitsu Hara, Ken Kijima, Takeshi Maeda, Hiroyuki Katoh, Yasuyuki Ohkawa, Yasuharu Nakashima, Seiji Okada
Traumatic spinal cord injury (SCI) causes serious disruption of neuronal circuits that leads to motor functional deficits. Regeneration of disrupted circuits back to their original target is necessary for the restoration of function after SCI, but the pathophysiological condition of the caudal spinal cord has not been sufficiently studied. Here we investigated the histological and biological changes in the distal part of the injured spinal cord, using a mice model of complete thoracic SCI in the chronic stage (3 months after injury)...
January 9, 2019: Molecular Brain
Jianming Li
Traumatic injury to the spinal cord remains a catastrophic event that has lifelong consequences. While decades of research have elucidated much of the pathophysiology associated with spinal cord injury (SCI), there still remains no clinically approved treatments for restoring lost sensorimotor function. The traditional dogma suggests central nervous system (CNS) neurons do not regenerate after injury but active areas of research aim to overcome this biological bottleneck. One particular approach using low-level direct current electric fields (DC EFs) appears especially promising based on a rich set of experimental data...
January 4, 2019: Neurosurgical Review
Zahra Hassannejad, Shayan Abdollah Zadegan, Alexander R Vaccaro, Vafa Rahimi-Movaghar, Omid Sabzevari
BACKGROUND: The complex pathophysiological events occurring after traumatic spinal cord injuries (TSCI) make this devastating trauma still incurable. Peptide amphiphile (PA) hydrogels are nanobiomaterials displaying desirable properties for application in regenerative medicine because they are absorbable, injectable, allowing biofunctionalization, controlling release of trophic factors and mimic extracellular matrix (ECM). In this study, we explored the potentiality of the IKVAV-functionalized PA hydrogel to provide a permissive environment for cell migration and growth as well as sustained release of BDNF at the lesion after severe compression injury model...
December 19, 2018: Injury
Lijuan Xu, Qixing Wang, Wei Jiang, Shunzhi Yu, Shouqin Zhang
MicroRNAs have been reported to be an important pathophysiological factor in neuropathic pain. However, the potential mechanism through which miRNAs function in neuropathic pain remains unclear. The purpose of this study was to explore the potential role of mir-34c in neuropathic pain in a mouse model of chronic sciatic nerve injury (CCI). We found that overexpression of miR-34c greatly alleviated CCI-induced neuropathic pain and spinal cord infarction, and reduced cell apoptotic and inflammatory cytokine expression in CCI mice...
December 26, 2018: Neuroscience
Elspeth J R Hill, Ida K Fox
LEARNING OBJECTIVES: After reviewing this article, the participant should be able to: 1. Understand the anatomy and pathophysiology of spinal cord injury and the resulting upper and lower motor neuron syndromes. 2. Recognize who may benefit from nerve transfers. 3. Understand the role of history, examination, imaging, and electrodiagnostics in the determination of time-sensitive lower motor neuron injury versus non-time-sensitive upper motor neuron injury. 4. Outline the surgical options and perioperative care for those undergoing nerve transfer and the expected outcomes in restoring shoulder, elbow, wrist, and hand function...
January 2019: Plastic and Reconstructive Surgery
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
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