Molecular and cellular neurosciences · 2025
The role of alarmins in neuroinflammation following spinal cord injury: A systematic review of the literature.
СтатьяСистематический обзорНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Rajkovic Christian, MacElroy Donald, Spirollari Eris, Vazquez Sima, Subah Galadu, Lazzari Julianna, Zeller Sabrina L, Wainwright John V, Jhanwar-Uniyal Meena, Kinon Merritt D
Аннотация
BACKGROUND: Alarmins, or damage-associated molecular patterns (DAMPs), are a diverse class of molecules essential for cellular homeostasis; however, their activation following traumatic cell necrosis contributes to neuroinflammation leading to neurologic deficits. This review aims to highlight the current preclinical alarmin studies and define their neuroprotective role in the treatment of SCI.
METHODS: A systematic review was performed to evaluate studies investigating alarmin-mediated immune and neuroinflammatory responses following SCI in animal models. Primary outcomes investigated included immunostaining of cell lines, quantification of alarmin, cytokine, and inflammatory mediators, myelin staining, and animal function scores.
RESULTS: IL-1α, HMGB1, S100A1, MIF, D-DT, IL-33, heme, cell-free DNA, and extracellular nucleotides were found to act as alarmins in animal models of SCI. The expression of these molecules in neurons and neuroglia at the SCI lesion site increased levels of TNF-α, IL-1β, and iNOS, contributing to neuroinflammation. Induction of the neurotoxic phenotypes of macrophages, microglia, and astrocytes by IL-1α, HMGB1, and IL-33 promoted cell death and reduction in oligodendrocyte number. Inhibitors of alarmin-signaling pathways, such as toll-like receptors (TLRs), IL-1R1, RAGE, ST2, and mTOR improved neurological function, as shown by enhanced postoperative locomotion.
CONCLUSIONS: Elevated alarmin expression and activity at the SCI site contribute to functional deficits by augmenting neuroinflammation, cell death, and cytotoxic neuroglia. Targeting alarmin-mediated signaling pathways represents a promising therapeutic approach in SCI treatment.
METHODS: A systematic review was performed to evaluate studies investigating alarmin-mediated immune and neuroinflammatory responses following SCI in animal models. Primary outcomes investigated included immunostaining of cell lines, quantification of alarmin, cytokine, and inflammatory mediators, myelin staining, and animal function scores.
RESULTS: IL-1α, HMGB1, S100A1, MIF, D-DT, IL-33, heme, cell-free DNA, and extracellular nucleotides were found to act as alarmins in animal models of SCI. The expression of these molecules in neurons and neuroglia at the SCI lesion site increased levels of TNF-α, IL-1β, and iNOS, contributing to neuroinflammation. Induction of the neurotoxic phenotypes of macrophages, microglia, and astrocytes by IL-1α, HMGB1, and IL-33 promoted cell death and reduction in oligodendrocyte number. Inhibitors of alarmin-signaling pathways, such as toll-like receptors (TLRs), IL-1R1, RAGE, ST2, and mTOR improved neurological function, as shown by enhanced postoperative locomotion.
CONCLUSIONS: Elevated alarmin expression and activity at the SCI site contribute to functional deficits by augmenting neuroinflammation, cell death, and cytotoxic neuroglia. Targeting alarmin-mediated signaling pathways represents a promising therapeutic approach in SCI treatment.