Neuroinflammation after SCI: Current Insights and Therapeutic Potential of Intravenous Immunoglobulin

Gillespie, Ellen R.; Ruitenberg, Marc J.

doi:10.1089/neu.2019.6952

Cited by 11 publications

(12 citation statements)

References 142 publications

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“…Traumatic spinal cord injury (SCI) is hallmarked by a chronic, non‐resolving inflammatory response at the lesion site that involves both CNS‐resident and infiltrating white blood cells (WBCs) 1,2 . Although reparative aspects have been ascribed to at least some aspects of inflammation after SCI, 3–5 on balance, the inflammatory response is thought to be maladaptive and an amplifier of secondary pathology in spared spinal cord tissue 6 . Numerous experimental animal studies, mostly conducted in rodents, have provided a detailed description of the spatiotemporal development of the cellular inflammatory response to SCI (reviewed by Gillespie and Ruitenberg 6 ), the key features of which are recapitulated in human patients 7 .…”

Section: Introductionmentioning

confidence: 99%

“…1,2 Although reparative aspects have been ascribed to at least some aspects of inflammation after SCI, [3][4][5] on balance, the inflammatory response is thought to be maladaptive and an amplifier of secondary pathology in spared spinal cord tissue. 6 Numerous experimental animal studies, mostly conducted in rodents, have provided a detailed description of the spatiotemporal development of the cellular inflammatory response to SCI (reviewed by Gillespie and Ruitenberg 6 ), the key features of which are recapitulated in human patients. 7 Neutrophils and monocytes dominate in the early inflammatory infiltrate at the site of SCI, and hence these cells continue to be intensely investigated as possible targets for immunomodulation.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic value of early leukocyte fluctuations for recovery from traumatic spinal cord injury

Jogia

Lübstorf

Jacobson

et al. 2021

Clinical & Translational Med

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We describe the systemic white blood cell (WBC) response to human spinal cord injury (SCI) and demonstrate how this is influenced by overall trauma severity, lesion level, and neurological grade on admission. We identify acute neutrophilia as a negative predictor for patient outcomes, the occurrence of which reduces the likelihood of American Spinal Injury Association Impairment Scale (AIS) grade conversion. We further show that lymphopenia during the first week of SCI is typically associated with better recovery, but that higher neutrophil to lymphocyte ratios early after SCI are associated with infection presentation in at-risk patients. Collectively, the multi-factorial models described in this work allow for better patient stratification and more accurate prediction of their outcomes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic value of early leukocyte fluctuations for recovery from traumatic spinal cord injury

Jogia

Lübstorf

Jacobson

et al. 2021

Clinical & Translational Med

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“…At SCI lesion site, the activation and invasion of immune cells and production of pro-inflammatory and pro-apoptotic molecule aggravated cell apoptosis and necrosis and amplified tissue loss [4,48]. The persisted pro-inflammatory responses hindered functional recovery.…”

Section: Discussionmentioning

confidence: 99%

Optimized, visible light-induced crosslinkable hybrid gelatin/hyaluronic acid scaffold promotes complete spinal cord injury repair

et al. 2022

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Severe microenvironmental changes after spinal cord injury (SCI) present serious challenges in neural regeneration and tissue repair. Gelatin (GL)- and hyaluronic acid (HA)-based hydrogels are attractive scaffolds because they are major components of the extracellular matrix and can provide a favorable adjustable microenvironment for neurogenesis and motor function recovery. In this study, three-dimensional hybrid GL/HA hydrogel scaffolds were prepared and optimized. The hybrid hydrogels could undergo in-situ gelation and fit the defects perfectly via visible light- induced crosslinking in the complete SCI rats. We found that the transplantation of the hybrid hydrogel scaffold significantly reduced the inflammatory responses and suppressed glial scar formation in an HA concentration-dependent manner. Moreover, the hybrid hydrogel with GL/HA ratios less than 8/2 effectively promoted endogenous neural stem cell migration and neurogenesis, as well as improved neuron maturation and axonal regeneration. The results showed locomotor function improved 60 days after transplantation, thus suggesting that GL/HA hydrogels can be considered as a promising scaffold for complete SCI repair.

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“…Inflammatory reaction after SCI is thus the most important pathological process to address during secondary injuries. Controlling excessive inflammation has been shown to improve the prognosis of SCI both clinically and in animals, as evidenced by accumulating reports (Gillespie and Ruitenberg, 2022;Zhang et al, 2022;Zhou et al, 2022b).…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture Relieves HuR/KLF9-Mediated Inflammation to Enhance Neurological Repair after Spinal Cord Injury

Zhang,

Xu,

et al. 2023

eNeuro

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Electroacupuncture (EA) is widely applied in clinical therapy for spinal cord injury (SCI). However, the associated molecular mechanism has yet to be elucidated. The current study aimed to investigate the underlying mechanism of EA in neurologic repair after SCI. First, we investigated the role of EA in the neurologic repair of the SCI rat model. The expression levels of human antigen R (HuR) and Krüppel-like factor 9 (KLF9) in spinal cord tissues were quantified after treatment. Second, we conducted bioinformatics analysis, RNA pull-down assays, RNA immunoprecipitation, and luciferase reporter gene assay to verify the binding of HuR and KLF9 mRNA for mRNA stability. Last, HuR inhibitor CMLD-2 was used to verify the enhanced effect of EA on neurologic repair after SCI via the HuR/KLF9 axis. Our data provided convincing evidence that EA facilitated the recovery of neuronal function in SCI rats by reducing apoptosis and inflammation of neurons. We found that EA significantly diminished the SCI-mediated upregulation of HuR, and HuR could bind to the 3′ untranslated region of KLF9 mRNA to protect its decay. In addition, a series ofin vivoexperiments confirmed that CMLD-2 administration increased EA-mediated pain thresholds and motor function in SCI rats. Collectively, the present study showed that EA improved pain thresholds and motor function in SCI rats via impairment of HuR-mediated KLF9 mRNA stabilization, thus providing a better understanding of the regulatory mechanisms regarding EA-mediated neurologic repair after SCI.

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Neuroinflammation after SCI: Current Insights and Therapeutic Potential of Intravenous Immunoglobulin

Cited by 11 publications

References 142 publications

Prognostic value of early leukocyte fluctuations for recovery from traumatic spinal cord injury

Prognostic value of early leukocyte fluctuations for recovery from traumatic spinal cord injury

Optimized, visible light-induced crosslinkable hybrid gelatin/hyaluronic acid scaffold promotes complete spinal cord injury repair

Electroacupuncture Relieves HuR/KLF9-Mediated Inflammation to Enhance Neurological Repair after Spinal Cord Injury

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