scholarly journals Acute IL-1RA treatment suppresses the peripheral and central inflammatory response to spinal cord injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Abi G. Yates ◽  
Trisha Jogia ◽  
Ellen R. Gillespie ◽  
Yvonne Couch ◽  
Marc J. Ruitenberg ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Neutrophil Infiltration ◽  
Therapeutic Window ◽  
Marker Genes ◽  
Injured Spinal Cord ◽  
Lesion Site ◽  
Hepatic Expression ◽  
Cord Injury

Abstract Background The acute phase response (APR) to CNS insults contributes to the overall magnitude and nature of the systemic inflammatory response. Aspects of this response are thought to drive secondary inflammatory pathology at the lesion site, and suppression of the APR can therefore afford some neuroprotection. In this study, we examined the APR in a mouse model of traumatic spinal cord injury (SCI), along with its relationship to neutrophil recruitment during the immediate aftermath of the insult. We specifically investigated the effect of IL-1 receptor antagonist (IL-1RA) administration on the APR and leukocyte recruitment to the injured spinal cord. Methods Adult female C57BL/6 mice underwent either a 70kD contusive SCI, or sham surgery, and tissue was collected at 2, 6, 12, and 24 hours post-operation. For IL-1RA experiments, SCI mice received two intraperitoneal injections of human IL-1RA (100mg/kg), or saline as control, immediately following, and 5 hours after impact, and animals were sacrificed 6 hours later. Blood, spleen, liver and spinal cord were collected to study markers of central and peripheral inflammation by flow cytometry, immunohistochemistry and qPCR. Results were analysed by two-way ANOVA or student’s t-test, as appropriate. Results SCI induced a robust APR, hallmarked by elevated hepatic expression of pro-inflammatory marker genes and a significantly increased neutrophil presence in the blood, liver and spleen of these animals, as early as 2 hours after injury. This peripheral response preceded significant neutrophil infiltration of the spinal cord, which peaked 24 hours post-SCI. Although expression of IL-1RA was also induced in the liver following SCI, its response was delayed compared to IL-1β. Exogenous administration of IL-1RA during this putative therapeutic window was able to suppress the hepatic APR, as evidenced by a reduction in CXCL1 and SAA-2 expression as well as a significant decrease in neutrophil infiltration in both the liver and the injured spinal cord itself. Conclusions Our data indicate that peripheral administration of IL-1RA can attenuate the APR which in turn reduces immune cell infiltration at the spinal cord lesion site. We propose IL-1RA treatment as a viable therapeutic strategy to minimise the harmful effects of SCI-induced inflammation.

scholarly journals Splenic sympathetic signaling contributes to acute neutrophil infiltration of the injured spinal cord

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Susana Monteiro ◽  
Andreia G. Pinho ◽  
Mara Macieira ◽  
Cláudia Serre-Miranda ◽  
Jorge R. Cibrão ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Neutrophil Infiltration ◽  
Innate Immune ◽  
Injured Spinal Cord ◽  
Post Injury ◽  
Cord Injury ◽  
Immune Changes

Abstract Background Alterations in the immune system are a complication of spinal cord injury (SCI) and have been linked to an excessive sympathetic outflow to lymphoid organs. Still unknown is whether these peripheral immune changes also contribute for the deleterious inflammatory response mounted at the injured spinal cord. Methods We analyzed different molecular outputs of the splenic sympathetic signaling for the first 24 h after a thoracic compression SCI. We also analyzed the effect of ablating the splenic sympathetic signaling to the innate immune and inflammatory response at the spleen and spinal cord 24 h after injury. Results We found that norepinephrine (NE) levels were already raised at this time-point. Low doses of NE stimulation of splenocytes in vitro mainly affected the neutrophils’ population promoting an increase in both frequency and numbers. Interestingly, the interruption of the sympathetic communication to the spleen, by ablating the splenic nerve, resulted in reduced frequencies and numbers of neutrophils both at the spleen and spinal cord 1 day post-injury. Conclusion Collectively, our data demonstrates that the splenic sympathetic signaling is involved in the infiltration of neutrophils after spinal cord injury. Our findings give new mechanistic insights into the dysfunctional regulation of the inflammatory response mounted at the injured spinal cord.

MiRNA-194-5p inhibits inflammatory response after spinal cord injury via regulating TRAF6

2020 ◽  
Vol 111 (6) ◽  
Author(s):  
Siyuan Chen ◽  
Jinsong Wei ◽  
Liumei Huang ◽  
Bolin Feng ◽  
Weixiong Guo
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Cord Injury

Polyphenols as Potential Therapeutics for Pain and Inflammation in Spinal Cord Injury

2020 ◽  
Vol 13 ◽  
Author(s):  
Ashif Iqubal ◽  
Musheer Ahmed ◽  
Mohammad Kashif Iqubal ◽  
Faheem Hyder Pottoo ◽  
Syed Ehtaishamul Haque
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Side Effects ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Neutrophil Infiltration ◽  
Matrix Metal ◽  
Mediators Of Inflammation ◽  
Major Player ◽  
Cord Injury

: Spinal cord injury (SCI) and associated pain and inflammation caused by the trauma or infection is one of the serious health care issues world-wide. The various inflammatory, redox-sensitive and apoptotic events are contributing factor but altered neuronal function, axonal degeneration, activated microglia, endothelial cells, astrocytes, fibroblasts,pericytes, Schwann cells, meningeal cells are the major player in its pathogenesis. Further, monocytes and neutrophil infiltration get recruited and facilitate the release of chemokines, cytokines, and other mediators of inflammation. This event leads to the production of different amino acids, neuropeptides kinin, prostaglandins, prostacyclin, thromboxane, leukotrienes, bradykinin, histamine, matrix metal proteinases and serotonin that stimulate nerve endings and manifests the inflammation and pain processes, etc. Arachidonic acid (AA), NF-kB, NLRP3 inflammasome, and nitric oxide pathways along with P2X7 receptor and ion channel transient receptor potential (TRP) vanilloid are some of the recently explored targets for modulation of pain and inflammation in SCI. Till now, NSAIDs, opioids, antidepressants, anticonvulsants, NMDA antagonists, α2-adrenergic agonists, and GABA-receptor agonists are used for the management of these pathological conditions. However, these drugs are associated with various side effects. Additionally, the number of available animal models for SCI has enhanced the understanding of the complex pathological mechanisms involved in the generation of chronic inflammatory pain in SCI. These findings enable us to identify and validate several potent natural analgesic-anti-inflammatory drug candidates with minimal side effects. However, until now, these compounds have been studied in preclinical models and shown promising results but no clinical studies have been performed. Therefore, a detailed exploration of these natural compounds is important for bringing them from bench to bedside.

scholarly journals Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

Inflammation ◽  
2021 ◽  
Author(s):  
Shangrila Parvin ◽  
Clintoria R. Williams ◽  
Simone A. Jarrett ◽  
Sandra M. Garraway
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokine ◽  
Cardiovascular Health ◽  
Mrna Levels ◽  
Post Injury ◽  
Cord Injury ◽  
And Function ◽  
The Impact

Abstract— Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.

scholarly journals Knockdown of long non-coding RNA NEAT1 relieves the inflammatory response of spinal cord injury through targeting miR-211-5p/MAPK1 axis

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 2702-2712
Author(s):  
Qing An ◽  
Zipeng Zhou ◽  
Yi Xie ◽  
Yu Sun ◽  
Haixiang Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Non Coding Rna ◽  
Cord Injury ◽  
Long Non Coding Rna

The therapeutic window for spinal cord decompression in a rat spinal cord injury model

2005 ◽  
Vol 3 (4) ◽  
pp. 302-307 ◽  
Author(s):  
Christopher B. Shields ◽  
Y. Ping Zhang ◽  
Lisa B. E. Shields ◽  
Yingchun Han ◽  
Darlene A. Burke ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Stenosis ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Therapeutic Window ◽  
Content Type ◽  
Significant Difference ◽  
Cord Injury ◽  
Fine Print

Object. There are no clinically based guidelines to direct the spine surgeon as to the proper timing to undertake decompression after spinal cord injury (SCI) in patients with concomitant stenosis-induced cord compression. The following three factors affect the prognosis: 1) severity of SCI; 2) degree of extrinsic spinal cord compression; and 3) duration of spinal cord compression. Methods. To elucidate further the relationship between varying degrees of spinal stenosis and a mild contusion-induced SCI (6.25 g-cm), a rat SCI/stenosis model was developed in which 1.13- and 1.24-mm-thick spacers were placed at T-10 to create 38 and 43% spinal stenosis, respectively. Spinal cord damage was observed after the stenosis—SCI that was directly proportional to the duration of spinal cord compression. The therapeutic window prior to decompression was 6 and 12 hours in the 43 and 38% stenosis—SCI lesions, respectively, to maintain locomotor activity. A significant difference in total lesion volume was observed between the 2-hour and the delayed time(s) to decompression (38% stenosis—SCI, 12 and 24 hours, p < 0.05; 43% stenosis—SCI, 24 hours, p < 0.05) indicating a more favorable neurological outcome when earlier decompression is undertaken. This finding was further supported by the animal's ability to support weight when decompression was performed by 6 or 12 hours compared with 24 hours after SCI. Conclusions. Analysis of the findings in this study suggests that early decompression in the rat improves locomotor function. Prolongation of the time to decompression may result in irreversible damage that prevents locomotor recovery.

scholarly journals Overexpression of Rictor in the injured spinal cord promotes functional recovery in a rat model of spinal cord injury

2020 ◽  
Vol 34 (5) ◽  
pp. 6984-6998
Author(s):  
Ningning Chen ◽  
Pengxiang Zhou ◽  
Xizhe Liu ◽  
Jiachun Li ◽  
Yong Wan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Rat Model ◽  
Injured Spinal Cord ◽  
Cord Injury
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