scholarly journals Conditional Ablation of Myeloid TNF Improves Functional Outcome and Decreases Lesion Size after Spinal Cord Injury in Mice

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2407
Author(s):  
Ditte Gry Ellman ◽  
Minna Christiansen Lund ◽  
Maiken Nissen ◽  
Pernille Sveistrup Nielsen ◽  
Charlotte Sørensen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Outcome ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Lesion Size ◽  
Signaling Cascades ◽  
Lesion Volume ◽  
Cord Injury ◽  
Cytokine Tumor Necrosis Factor

Spinal cord injury (SCI) is a devastating condition consisting of an instant primary mechanical injury followed by a secondary injury that progresses for weeks to months. The cytokine tumor necrosis factor (TNF) plays an important role in the pathophysiology of SCI. We investigated the effect of myeloid TNF ablation (peripheral myeloid cells (macrophages and neutrophils) and microglia) versus central myeloid TNF ablation (microglia) in a SCI contusion model. We show that TNF ablation in macrophages and neutrophils leads to reduced lesion volume and improved functional outcome after SCI. In contrast, TNF ablation in microglia only or TNF deficiency in all cells had no effect. TNF levels tended to be decreased 3 h post-SCI in mice with peripheral myeloid TNF ablation and was significantly decreased 3 days after SCI. Leukocyte and microglia populations and all other cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, and IFNγ) and chemokines (CCL2, CCL5, and CXCL1) investigated, in addition to TNFR1 and TNFR2, were comparable between genotypes. Analysis of post-SCI signaling cascades demonstrated that the MAPK kinase SAPK/JNK decreased and neuronal Bcl-XL levels increased post-SCI in mice with ablation of TNF in peripheral myeloid cells. These findings demonstrate that peripheral myeloid cell-derived TNF is pathogenic in SCI.

scholarly journals Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Ditte Gry Ellman ◽  
Matilda Degn ◽  
Minna Christiansen Lund ◽  
Bettina Hjelm Clausen ◽  
Hans Gram Novrup ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lesion Size ◽  
Dominant Negative ◽  
Lesion Volume ◽  
Epidural Administration ◽  
Genetic Ablation ◽  
Cord Injury ◽  
Dominant Negative Inhibitor ◽  
Cytokine Tumor Necrosis Factor

Traumatic spinal cord injury (SCI) is followed by an instant increase in expression of the microglial-derived proinflammatory cytokine tumor necrosis factor (TNF) within the lesioned cord. TNF exists both as membrane-anchored TNF (mTNF) and as cleaved soluble TNF (solTNF). We previously demonstrated that epidural administration of a dominant-negative inhibitor of solTNF, XPro1595, to the contused spinal cord resulted in changes in Iba1 protein expression in microglia/macrophages, decreased lesion volume, and improved locomotor function. Here, we extend our studies using mice expressing mTNF, but no solTNF (mTNFΔ/Δ), to study the effect of genetic ablation of solTNF on SCI. We demonstrate that TNF levels were significantly decreased within the lesioned spinal cord 3 days after SCI inmTNFΔ/Δmice compared to littermates. This decrease did, however, not translate into significant changes in other pro- and anti-inflammatory cytokines (IL-10, IL-1β, IL-6, IL-5, IL-2, CXCL1, CCL2, or CCL5), despite a tendency towards increased IL-10 and decreased IL-1β, TNFR1, and TNFR2 levels inmTNFΔ/Δmice. In addition, microglial and leukocyte infiltration, activation state (Iba1, CD11b, CD11c, CD45, and MHCII), lesion size, and functional outcome after moderate SCI were comparable between genotypes. Collectively, our data demonstrate that genetic ablation of solTNF does not significantly modulate postlesion outcome after SCI.

scholarly journals A Clinical Prediction Model for Long-Term Functional Outcome after Traumatic Spinal Cord Injury Based on Acute Clinical and Imaging Factors

2012 ◽  
Vol 29 (13) ◽  
pp. 2263-2271 ◽  
Author(s):  
Jefferson R. Wilson ◽  
Robert G. Grossman ◽  
Ralph F. Frankowski ◽  
Alexander Kiss ◽  
Aileen M. Davis ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Prediction Model ◽  
Functional Outcome ◽  
Traumatic Spinal Cord Injury ◽  
Clinical Prediction ◽  
Clinical Prediction Model ◽  
Cord Injury

scholarly journals Tamoxifen attenuates inflammatory-mediated damage and improves functional outcome after spinal cord injury in rats

2009 ◽  
Vol 109 (6) ◽  
pp. 1658-1667 ◽  
Author(s):  
Dai-Shi Tian ◽  
Jun-Li Liu ◽  
Min-Jie Xie ◽  
Yan Zhan ◽  
Wen-Sheng Qu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Outcome ◽  
Cord Injury

scholarly journals Beneficial Effect of the Traditional Chinese Drug Shu-Xue-Tong on Recovery of Spinal Cord Injury in the Rat

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Li-Yun Jia ◽  
An-Hui Yao ◽  
Fang Kuang ◽  
Yu-Kai Zhang ◽  
Xue-Feng Shen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Blood Flow ◽  
Histological Analysis ◽  
Lesion Size ◽  
Chinese Drug ◽  
Sprague Dawley ◽  
Spinal Cord Blood Flow ◽  
Doppler Flowmetry ◽  
Cord Injury

Shu-Xue-Tong (SXT) is a traditional Chinese drug widely used to ameliorate stagnation of blood flow, such as brain or myocardial infarction. Whether SXT may have therapeutic value for spinal cord injury (SCI), during which ischemia plays an important role in its pathology, remains to be elucidated. We hypothesized that SXT may promote SCI healing by improving spinal cord blood flow (SCBF), and a study was thus designed to explore this possibility. Twenty-five male Sprague-Dawley rats were used. SCI was induced by compression, and SXT was administrated 24 h postinjury for 14 successive days. The effects of SXT were assessed by means of laser-Doppler flowmetry, motor functional analysis (open-field walking and footprint analysis), and histological analysis (hematoxylin-eosin and thionin staining and NeuN immunohistochemistry). SXT significantly promoted SCBF of the contused spinal cord and enhanced the recovery of motor function. Histological analysis indicated that the lesion size was reduced, the pathological changes were ameliorated, and more neurons were preserved. Based on these results we conclude that SXT can effectively improve SCI.

scholarly journals Galantamine improves functional recovery and reduces lesion size in a rat model of spinal cord injury

2019 ◽  
Vol 1724 ◽  
pp. 146424 ◽  
Author(s):  
Laura E. Sperling ◽  
Karina Pires Reis ◽  
Fabricio Nicola ◽  
Cristian Euzebio Teixeira ◽  
Gabriele Gulielmin Didó ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Rat Model ◽  
Lesion Size ◽  
Cord Injury

scholarly journals CCL3 contributes to secondary damage after spinal cord injury

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Nicolas Pelisch ◽  
Jose Rosas Almanza ◽  
Kyle E. Stehlik ◽  
Brandy V. Aperi ◽  
Antje Kroner
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Lesion Size ◽  
Secondary Injury ◽  
Wild Type ◽  
Locomotor Recovery ◽  
Secondary Damage ◽  
Cord Injury

Abstract Background Secondary damage after spinal cord injury (SCI) is characterized by a cascade of events including hemorrhage, apoptosis, oxidative stress, and inflammation which increase the lesion size which can influence the functional impairment. Thus, identifying specific mechanisms attributed to secondary injury is critical in minimizing tissue damage and improving neurological outcome. In this work, we are investigating the role of CCL3 (macrophage inflammatory protein 1-α, MIP-1α), a chemokine involved in the recruitment of inflammatory cells, which plays an important role in inflammatory conditions of the central and peripheral nervous system. Methods A mouse model of lower thoracic (T11) spinal cord contusion injury was used. We assessed expression levels of CCL3 and its receptors on the mRNA and protein level and analyzed changes in locomotor recovery and the inflammatory response in the injured spinal cord of wild-type and CCL3−/− mice. Results The expression of CCL3 and its receptors was increased after thoracic contusion SCI in mice. We then examined the role of CCL3 after SCI and its direct influence on the inflammatory response, locomotor recovery and lesion size using CCL3−/− mice. CCL3−/− mice showed mild but significant improvement of locomotor recovery, a smaller lesion size and reduced neuronal damage compared to wild-type controls. In addition, neutrophil numbers as well as the pro-inflammatory cytokines and chemokines, known to play a deleterious role after SCI, were markedly reduced in the absence of CCL3. Conclusion We have identified CCL3 as a potential target to modulate the inflammatory response and secondary damage after SCI. Collectively, this study shows that CCL3 contributes to progressive tissue damage and functional impairment during secondary injury after SCI.

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