Astrocyte- and Neuron-Derived CXCL1 Drives Neutrophil Transmigration and Blood-Brain Barrier Permeability in Viral Encephalitis

Michael, Benedict; Bricio-Moreno, Laura; Sorensen, Elizabeth W.; Miyabe, Yoshishige; Lian, Jeffrey; Solomon, Tom; Kurt-Jones, Evelyn A.; Luster, Andrew D.

doi:10.1016/j.celrep.2020.108150

Cited by 81 publications

(82 citation statements)

References 78 publications

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“…For example, CCL5 is a chemoattractant of T cells to the site of in ammation, which mediates the cerebral in ammation and causes BBB disruption [39]. CXCL1 produced by astrocytes is a critical ligand required for neutrophil trans-endothelial migration and exacerbates brain damage [40].…”

Section: Discussionmentioning

confidence: 99%

Blocking A1 astrocyte conversion with semaglutide attenuates blood-brain barrier disruption in mice after middle cerebral artery occlusion

Zhang

Liu

Shi

et al. 2021

Preprint

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Background Astrocytes play an essential role in the modulation of blood-brain barrier function. Neurological diseases induce astrocytes to transform into a neurotoxic A1 phenotype, thus exacerbating brain injury. However, the effect of A1 astrocyte on the function of BBB after stroke is unknown. Method: Adult male ICR mice (n = 78) were subjected to 90-minute transient middle cerebral artery occlusion. Immunohistochemical staining of A1 (C3d) and A2 (S100A10) was performed to characterize phenotypic changes of astrocytes overtime after stroke. Glucagon-like peptide-1 receptor agonist semaglutide was intraperitoneally injected into the mice to inhibit A1 astrocyte. Infarct volume, atrophy volume, neurobehavioral outcomes, and BBB permeability were examined. RNA-seq was adopted to explore the potential targets and signaling pathways of A1 astrocytes induced BBB dysfunction. Results Astrocytes assumed the A2 phenotype at the early stage of ischemic stroke but gradually transformed to the A1 phenotype. Semaglutide treatment reduced M1 microglia polarization and A1 astrocytes conversion after ischemic stroke (p < 0.05). Ischemia induced brain infarct volume, atrophy volume and neuroinflammation were reduced in the semaglutide treated mice. Neurobehavioral outcomes were improved compared to the control mice (p < 0.05). Further study demonstrated that semaglutide treatment reduced the gap formation of tight junction proteins ZO-1, claudin-5 and occludin, as well as IgG leakage following three days of ischemic stroke (p < 0.05). In vitro experiments revealed that A1 astrocyte-conditioned medium disrupted BBB integrity. RNA-seq further showed that A1 astrocytes were enriched in inflammatory factors and chemokines, as well as significantly modulating TNF and chemokine signaling pathways, which are closely related to barrier damage. Conclusion We concluded that astrocytes undergo a conversion from A2 phenotype to A1 phenotype overtime after ischemic stroke. A1 astrocytes aggravated BBB disruption, suggesting that block of A1 astrocytes conversion provides a novel strategy for the treatment of ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Blocking A1 astrocyte conversion with semaglutide attenuates blood-brain barrier disruption in mice after middle cerebral artery occlusion

Zhang

Liu

Shi

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Expression of microRNAs (29a and 222) related to inhibition of autophagic signals is significantly enhanced [45][46][47], APP accumulated, together with increased expression of a p-ERK protein A p62 protein, can influence the balance of mitophagy [38], and ERK phosphorylation is a regulator of pro-inflammatory responses in AD pathogenesis [48]. Additionally, IL-6 is a pleiotropic cytokine that can act in both pro-and anti-inflammatory responses, and CCL-2 and CXCL-1 act for chemotaxis of monocytes and neutrophils, respectively [49]. Herein, we hypothesize that WCSC may cause accumulation of APP by blocking autophagic signals and contribute to the occurrence of AD due to deficiency in recruiting immune cells.…”

Section: Discussionmentioning

confidence: 99%

Whole Cigarette Smoke Condensates Induce Accumulation of Amyloid Beta Precursor Protein with Oxidative Stress in Murine Astrocytes

Park

Jin

Lim

et al. 2021

Toxics

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Although cigarette smoking has been postulated to be a potential risk factor for Alzheimer’s disease (AD), the toxic mechanism is still unclear. Additionally, astrocytes have been identified as a potential target, given they play multiple roles in maintaining normal brain function. In this study, we explored the toxic mechanism of whole cigarette smoke condensates (WCSC) using murine astrocytes. Cell proliferation, the percentage of cells in the G2/M phase, and LDH concentrations in the cell supernatants were all reduced in WCSC-treated cells. In addition, oxidative stress was induced, together with shortening of processes, structural damage of organelles, disturbances in mitochondrial function, blockage of autophagic signals, accumulation of amyloid β precursor protein, and loss of chemotactic functions. Based on these results, we hypothesize that dysfunction of astrocytes may contribute to the occurrence of cigarette-smoking-induced AD.

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“…These manifestations are observed in herpes simplex (HSV-1) infection associated with viral encephalitis. The chemokine (C-X-C motif) ligand 1 (CXCL1) is produced by astrocytes in response to HSV-1 and by astrocytes and neurons in response to IL-1α ( Michael et al., 2020 ) and forms part of the SARS-CoV-2 hyper-neuroinflammatory response. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)…”

Section: A Unifying Hypothesis Of Sars-cov-2 Affectation Of the Cnsmentioning

confidence: 99%

The unfolding palette of COVID-19 multisystemic syndrome and its neurological manifestations

Barrantes

2021

Brain, Behavior, & Immunity - Health

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Although our current knowledge of the pathophysiology of COVID-19 is still fragmentary, the information so far accrued on the tropism and life cycle of its etiological agent SARS-CoV-2, together with the emerging clinical data, suffice to indicate that the severe acute pulmonary syndrome is the main, but not the only manifestation of COVID-19. Necropsy studies are increasingly revealing underlying endothelial vasculopathies in the form of micro-haemorrhages and micro-thrombi. Intertwined with defective antiviral responses, dysregulated coagulation mechanisms, abnormal hyper-inflammatory reactions and responses, COVID-19 is disclosing a wide pathophysiological palette. An additional property in categorising the disease is the combination of tissue (e.g. neuro- and vasculo-tropism) with organ tropism, whereby the virus preferentially attacks certain organs with highly developed capillary beds, such as the lungs, gastrointestinal tract, kidney and brain. These multiple clinical presentations confirm that the acute respiratory syndrome as described initially is increasingly unfolding as a more complex nosological entity, a multiorgan syndrome of systemic breadth. The neurological manifestations of COVID-19, the focus of this review, reflect this manifold nature of the disease.

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Astrocyte- and Neuron-Derived CXCL1 Drives Neutrophil Transmigration and Blood-Brain Barrier Permeability in Viral Encephalitis

Cited by 81 publications

References 78 publications

Blocking A1 astrocyte conversion with semaglutide attenuates blood-brain barrier disruption in mice after middle cerebral artery occlusion

Blocking A1 astrocyte conversion with semaglutide attenuates blood-brain barrier disruption in mice after middle cerebral artery occlusion

Whole Cigarette Smoke Condensates Induce Accumulation of Amyloid Beta Precursor Protein with Oxidative Stress in Murine Astrocytes

The unfolding palette of COVID-19 multisystemic syndrome and its neurological manifestations

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