The MASCIS Spinal Cord Contusion Model

2019 ◽  
pp. 403-414
Author(s):  
Wise Young
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Contusion

scholarly journals D-dopachrome tautomerase activates COX2/PGE2 pathway of astrocytes to mediate inflammation following spinal cord injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Huiyuan Ji ◽  
Yuxin Zhang ◽  
Chen Chen ◽  
Hui Li ◽  
Bingqiang He ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signal Pathways ◽  
Post Injury ◽  
Dopachrome Tautomerase ◽  
Protein Levels ◽  
Cytokines And Chemokines ◽  
Cord Injury ◽  
Mitogen Activated Protein ◽  
Spinal Cord Contusion

Abstract Background Astrocytes are the predominant glial cell type in the central nervous system (CNS) that can secrete various cytokines and chemokines mediating neuropathology in response to danger signals. D-dopachrome tautomerase (D-DT), a newly described cytokine and a close homolog of macrophage migration inhibitory factor (MIF) protein, has been revealed to share an overlapping function with MIF in some ways. However, its cellular distribution pattern and mediated astrocyte neuropathological function in the CNS remain unclear. Methods A contusion model of the rat spinal cord was established. The protein levels of D-DT and PGE2 synthesis-related proteinase were assayed by Western blot and immunohistochemistry. Primary astrocytes were stimulated by different concentrations of D-DT in the presence or absence of various inhibitors to examine relevant signal pathways. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results D-DT was inducibly expressed within astrocytes and neurons, rather than in microglia following spinal cord contusion. D-DT was able to activate the COX2/PGE2 signal pathway of astrocytes through CD74 receptor, and the intracellular activation of mitogen-activated protein kinases (MAPKs) was involved in the regulation of D-DT action. The selective inhibitor of D-DT was efficient in attenuating D-DT-induced astrocyte production of PGE2 following spinal cord injury, which contributed to the improvement of locomotor functions. Conclusion Collectively, these data reveal a novel inflammatory activator of astrocytes following spinal cord injury, which might be beneficial for the development of anti-inflammation drug in neuropathological CNS.

Spatiotemporal CCR1, CCL3(MIP-1α), CXCR4, CXCL12(SDF-1α) expression patterns in a rat spinal cord injury model of posttraumatic neuropathic pain

2011 ◽  
Vol 14 (5) ◽  
pp. 583-597 ◽  
Author(s):  
Friederike Knerlich-Lukoschus ◽  
Beata von der Ropp-Brenner ◽  
Ralph Lucius ◽  
Hubertus Maximilian Mehdorn ◽  
Janka Held-Feindt
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Substance P ◽  
Time Course ◽  
Behavioral Testing ◽  
Dorsal Horns ◽  
Cord Injury ◽  
Dorsal Columns ◽  
Spinal Cord Contusion

Object Central neuropathic pain is a frequent challenging complication after spinal cord injury (SCI), and specific therapeutic approaches remain elusive. The purpose of the present investigations was to identify potential key mediators of these pain syndromes by analyzing detailed expression profiles of important chemokines in an experimental SCI paradigm of posttraumatic neuropathic pain in rats. Methods Expression of CCR1, CCL3(MIP-1α), CXCR4, and CXCL12(SDF-1α) was investigated in parallel with behavioral testing for mechanical and thermal nociceptive thresholds after standardized SCI; 100-kdyn (moderate injury) and 200-kdyn (severe injury) force-defined thoracic spinal cord contusion lesions were applied via an Infinite Horizon Impactor at the T-9 level. Sham controls received laminectomies. Hindlimb locomotor function as well as mechanical and thermal sensitivities were monitored weekly by standardized behavioral testing after SCI. Chemokine expression was analyzed by real-time reverse transcriptase polymerase chain reaction in the early (7 days postoperatively) and late (42 days postoperatively) time courses after SCI, and immunohistochemical analysis (anatomical and quantitative) was performed 2, 7, 14, and 42 days after lesioning. Double staining with cellular markers and pain-related peptides (substance P and CGRP) or receptors (TRPV-1, TRPV-2, VRL-1, and TLR-4) was performed. Based on data obtained from behavioral testing, quantified immunohistochemical chemokine expressions in individual animals were correlated with the respective mechanical and thermal sensitivity thresholds 6 weeks after SCI. Results After 200-kdyn lesions, the animals exhibited prolonged reduction in their nociceptive thresholds, while 100-kdyn groups showed pain-related behaviors only in the early time course after SCI. Investigated chemokines were widely induced after SCI, involving cervical, thoracic, and lumbar spinal cord levels far beyond the lesion core. CCR1 and CCL3 were induced significantly in the dorsal horns 2 days after lesioning and remained at high levels after SCI with significantly higher intensities after 200-kdyn than 100-kdyn contusions. CXCR4 and CXCL12 levels continuously increased from 2 to 42 days after moderate and severe lesions. Additionally, chemokines were induced significantly in dorsal columns, with highest density levels 42 days after 200-kdyn lesions. In dorsal horns, CCR1 was coexpressed with TRPV-1 while CXCR4 and CXCL12 were partially coexpressed with substance P and CGRP. In dorsal columns, CCL3/CCR1 colabeled with GFAP, TRPV-2, TRPV-1, TLR-4; CXCR4/CXCL12 coexpressed with GFAP, CD68/ED1, and TLR4. Chemokine immunoreactivity density levels, especially CCL3 and its receptor, correlated in part significantly with nociceptive thresholds. Conclusions The authors report lesion grade–dependent upregulation of different chemokines/chemokine receptors after spinal cord contusion lesions in pain-processing spinal cord regions in a clinically relevant model of traumatic SCI in rats. Prolonged chemokine induction further correlated with below-level pain development in the delayed time course after severe SCI and was coexpressed with pain-associated peptides and receptors, suggesting that chemokines play a crucial role in chronic central pain mechanisms after SCI.

Alterations in Burst Firing of Thalamic VPL Neurons and Reversal by Nav1.3 Antisense After Spinal Cord Injury

2006 ◽  
Vol 95 (6) ◽  
pp. 3343-3352 ◽  
Author(s):  
Bryan C. Hains ◽  
Carl Y. Saab ◽  
Stephen G. Waxman
Keyword(s):  
Spinal Cord ◽  
Receptive Fields ◽  
Burst Firing ◽  
Sprague Dawley ◽  
Abnormal Expression ◽  
Thoracic Level ◽  
Cord Injury ◽  
Single Spike ◽  
Spinal Cord Contusion ◽  
Firing Properties

We recently showed that spinal cord contusion injury (SCI) at the thoracic level induces pain-related behaviors and increased spontaneous discharges, hyperresponsiveness to innocuous and noxious peripheral stimuli, and enlarged receptive fields in neurons in the ventral posterolateral (VPL) nucleus of the thalamus. These changes are linked to the abnormal expression of Nav1.3, a rapidly repriming voltage-gated sodium channel. In this study, we examined the burst firing properties of VPL neurons after SCI. Adult male Sprague–Dawley rats underwent contusion SCI at the T9 level. Four weeks later, when Nav1.3 protein was upregulated within VPL neurons, extracellular unit recordings were made from VPL neurons in intact animals, those with SCI, and in SCI animals after receiving lumbar intrathecal injections of Nav1.3 antisense or mismatch oligodeoxynucleotides for 4 days. After SCI, VPL neurons with identifiable peripheral receptive fields showed rhythmic oscillatory burst firing with changes in discrete burst properties, and alternated among single-spike, burst, silent, and spindle wave firing modes. Nav1.3 antisense, but not mismatch, partially reversed alterations in burst firing after SCI. These results demonstrate several newly characterized changes in spontaneous burst firing properties of VPL neurons after SCI and suggest that abnormal expression of Nav1.3 contributes to these phenomena.

Gene expression alterations of neurotrophins, their receptors and prohormone convertases in a rat model of spinal cord contusion

2008 ◽  
Vol 441 (3) ◽  
pp. 261-266 ◽  
Author(s):  
Zahra Hajebrahimi ◽  
Seyed Javad Mowla ◽  
Mansureh Movahedin ◽  
Mahmoud Tavallaei
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Rat Model ◽  
Prohormone Convertases ◽  
Spinal Cord Contusion ◽  
Gene Expression Alterations

scholarly journals Automated Gait Analysis to Assess Functional Recovery in Rodents with Peripheral Nerve or Spinal Cord Contusion Injury

10.3791/61852 ◽  
2020 ◽  
Author(s):  
Johannes Heinzel ◽  
Nicole Swiadek ◽  
Mohamed Ashmwe ◽  
Alexander Rührnößl ◽  
Viola Oberhauser ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Peripheral Nerve ◽  
Gait Analysis ◽  
Functional Recovery ◽  
Contusion Injury ◽  
Spinal Cord Contusion

scholarly journals Proteomics and bioinformatics reveal insights into neuroinflammation in the acute to subacute phases in rat models of spinal cord contusion injury

2021 ◽  
Vol 35 (7) ◽  
Author(s):  
Xin‐Qiang Yao ◽  
Zhong‐Yuan Liu ◽  
Jia‐Ying Chen ◽  
Zu‐Cheng Huang ◽  
Jun‐Hao Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Rat Models ◽  
Contusion Injury ◽  
Spinal Cord Contusion

Therapeutic effects of disulfiram in spinal cord contusion of rabbits

1985 ◽  
Vol 43 (3) ◽  
pp. 359-363
Author(s):  
Subramanian Gunasekaran ◽  
Stephen Rayle ◽  
Philip Weinstein ◽  
Jaroslav J. Vostal ◽  
Milos Chvapil
Keyword(s):  
Spinal Cord ◽  
Therapeutic Effects ◽  
Spinal Cord Contusion
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