Delayed administration of high dose human immunoglobulin G enhances recovery after traumatic cervical spinal cord injury by modulation of neuroinflammation and protection of the blood spinal cord barrier

Chio, Jonathon Chon Teng; Wang, Jian; Surendran, Vithushan; Li, Lijun; Zavvarian, Mohammad-Masoud; Pieczonka, Katarzyna; Fehlings, Michael G.

doi:10.1016/j.nbd.2020.105187

Cited by 27 publications

(19 citation statements)

References 72 publications

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“…In support of this, we plotted expression of a major pro-inflammatory factor, TNFα, 20 and found that after the first rise there appeared to be a second rise occurring after 2 weeks post-injury (Supplementary Fig. 2c ), which was also reported by Chio et al 21 …”

Section: Resultssupporting

confidence: 83%

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Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury

Zhou

et al. 2022

Sig Transduct Target Ther

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Spinal cord injury (SCI) involves diverse injury responses in different cell types in a temporally and spatially specific manner. Here, using single-cell transcriptomic analyses combined with classic anatomical, behavioral, electrophysiological analyses, we report, with single-cell resolution, temporal molecular and cellular changes in crush-injured adult mouse spinal cord. Data revealed pathological changes of 12 different major cell types, three of which infiltrated into the spinal cord at distinct times post-injury. We discovered novel microglia and astrocyte subtypes in the uninjured spinal cord, and their dynamic conversions into additional stage-specific subtypes/states. Most dynamic changes occur at 3-days post-injury and by day-14 the second wave of microglial activation emerged, accompanied with changes in various cell types including neurons, indicative of the second round of attacks. By day-38, major cell types are still substantially deviated from uninjured states, demonstrating prolonged alterations. This study provides a comprehensive mapping of cellular/molecular pathological changes along the temporal axis after SCI, which may facilitate the development of novel therapeutic strategies, including those targeting microglia.

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Section: Resultssupporting

confidence: 83%

“…Interestingly, these data were consistent with already published studies using mouse and rat SCI models, as well as other studies on the temporal cellular and molecular changes after SCI in rodents, indicative of conservation of molecular and cellular pathophysiology after SCI. 9 , 10 , 21 , 39 …”

Section: Discussionmentioning

confidence: 99%

Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury

Zhou

et al. 2022

Sig Transduct Target Ther

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“…Most publications were from China (53%), while the rest were conducted in Korea and Canada. Except for one study ( Chio et al, 2021 ), all studies used Sprague Dawley rats as experimental animal models, although some rats were of different sexes. SCI was induced between T8 and T10 in every study except one ( Chio et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…Except for one study ( Chio et al, 2021 ), all studies used Sprague Dawley rats as experimental animal models, although some rats were of different sexes. SCI was induced between T8 and T10 in every study except one ( Chio et al, 2021 ). Although SCI was induced in all studies, the method used varied across different studies; 50% of studies used contusion, while the other 50% used compression.…”

Section: Resultsmentioning

confidence: 99%

Experimental treatments to attenuate blood spinal cord barrier rupture in rats with traumatic spinal cord injury: A meta-analysis and systematic review

Deng

Sun

2022

Front. Pharmacol.

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Background: Traumatic spinal cord injury (t-SCI) is a severe injury that has a devastating impact on neurological function. Blood spinal cord barrier (BSCB) destruction following SCI aggravates the primary injury, resulting in a secondary injury. A series of experimental treatments have been proven to alleviate BSCB destruction after t-SCI.Methods: From a screen of 1,189 papers, which were retrieved from Pubmed, Embase, and Web of science, we identified 28 papers which adhered to strict inclusion and exclusion criteria. Evans blue (EB) leakage on the first day post-SCI was selected as the primary result. Secondary outcomes included the expression of tight junction (TJ) proteins and adhesion junction (AJ) proteins in protein immunoblotting. In addition, we measured functional recovery using the Basso, Beattie, Besnahan (BBB) score and we analyzed the relevant mechanisms to explore the similarities between different studies.Result: The forest plot of Evans blue leakage (EB leakage) reduction rate: the pooled effect size of the 28 studies was 0.54, 95% CI: 0.47–0.61, p < 0.01. This indicates that measures to mitigate BSCB damage significantly improved in reducing overall EB leakage. In addition TJ proteins (Occludin, Claudin-5, and ZO-1), AJ proteins (P120 and β-catenin) were significantly upregulated after treatment in all publications. Moreover, BBB scores were significantly improved. Comprehensive studies have shown that in t-SCI, inhibition of matrix metalloproteinases (MMPs) is the most commonly used mechanism to mitigate BSCB damage, followed by endoplasmic reticulum (ER) stress and the Akt pathway. In addition, we found that bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos), which inhibit the TIMP2/MMP signaling pathway, may be the most effective way to alleviate BSCB injury.Conclusion: This study systematically analyzes the experimental treatments and their mechanisms for reducing BSCB injury in the early stage of t-SCI. BMSC-Exos, which inhibit MMP expression, are currently the most effective therapeutic modality for alleviating BSCB damage. In addition, the regulation of MMPs in particular as well as the Akt pathway and the ER stress pathway play important roles in alleviating BSCB injury.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324794.

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“…The inflammatory response plays critical roles in all the mechanisms of secondary injury and directly influences the neurological outcome post-injury. 56 Neuroinflammation was previously regarded as an adverse consequence after SCI because it led to a broader range of destructive processes including widespread healthy spinal cord tissue damage and further neuronal degeneration. With substantial advances in the understanding of SCI pathophysiology, it was gradually revealed that the early inflammatory response could also generate a permissive microenvironment for the regeneration of damaged neurons and axons, similar to early inflammatory benefits in other tissues.…”

Section: Contribution Of Distinct Immune Cells To Sci Inflammationmentioning

confidence: 99%

Regulatory Role of Mesenchymal Stem Cells on Secondary Inflammation in Spinal Cord Injury

QM¹,

Sy²,

SP³

et al. 2022

JIR

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Spinal cord injury (SCI) is a catastrophic condition with high morbidity and mortality that still lacks effective therapeutic strategies. It is well known that the most important stage in SCI pathogenesis is secondary injury, and among the involved mechanisms, the inflammatory cascade is the main contributor and directly influences neurological function recovery. In recent years, increasing evidence has shown that mesenchymal stem cells (MSCs) transplantation is a promising immunomodulatory strategy. Transplanted MSCs can regulate macrophage-, astrocyte-, and T lymphocyte-mediated neuroinflammation and help create a microenvironment that facilitates tissue repair and regeneration. This review focuses on the effects of different types of immune cells and MSCs, specifically the immunoregulatory capacity of MSCs in SCI and repair. We will also discuss how to exploit MSCs transplantation to regulate immune cells and develop novel therapeutic strategies for SCI.

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Delayed administration of high dose human immunoglobulin G enhances recovery after traumatic cervical spinal cord injury by modulation of neuroinflammation and protection of the blood spinal cord barrier

Cited by 27 publications

References 72 publications

Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury

Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury

Experimental treatments to attenuate blood spinal cord barrier rupture in rats with traumatic spinal cord injury: A meta-analysis and systematic review

Regulatory Role of Mesenchymal Stem Cells on Secondary Inflammation in Spinal Cord Injury

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