Border-associated macrophages in the central nervous system DOI Creative Commons
Rui Sun, Haowu Jiang

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Март 13, 2024

Abstract Tissue-resident macrophages play an important role in the local maintenance of homeostasis and immune surveillance. In central nervous system (CNS), brain are anatomically divided into parenchymal microglia non-parenchymal border-associated (BAMs). Among these cell populations, have been well-studied for their roles during development as well health disease. BAMs, mostly located choroid plexus, meningeal perivascular spaces, now gaining increased attention due to advancements multi-omics technologies genetic methodologies. Research on BAMs over past decade has focused ontogeny, immunophenotypes, involvement various CNS diseases, potential therapeutic targets. Unlike microglia, display mixed origins distinct self-renewal capacity. believed regulate neuroimmune responses associated with barriers contribute immune-mediated neuropathology. Notably, observed function diverse cerebral pathologies, including Alzheimer’s disease, Parkinson’s multiple sclerosis, ischemic stroke, gliomas. The elucidation heterogeneity functions neuroinflammation is mesmerizing, since it may shed light precision medicine that emphasizes deep insights programming cues unique microenvironment. this review, we delve latest findings covering aspects like origins, capacity, adaptability, implications different disorders.

Язык: Английский

Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner DOI Creative Commons
Emily F. Willis, Kelli P. A. MacDonald, Quan Nguyen

и другие.

Cell, Год журнала: 2020, Номер 180(5), С. 833 - 846.e16

Опубликована: Март 1, 2020

Язык: Английский

Процитировано

404
Pathophysiology and treatment of cerebral edema in traumatic brain injury DOI Creative Commons
Ruchira M. Jha, Patrick M. Kochanek, J. Marc Simard

и другие.

Neuropharmacology, Год журнала: 2018, Номер 145, С. 230 - 246

Опубликована: Авг. 4, 2018

Cerebral edema (CE) and resultant intracranial hypertension are associated with unfavorable prognosis in traumatic brain injury (TBI). CE is a leading cause of in-hospital mortality, occurring >60% patients mass lesions, ∼15% those normal initial computed tomography scans. After treatment lesions severe TBI, an important focus acute neurocritical care evaluating managing the secondary process hypertension. This review focuses on contemporary understanding various pathophysiologic pathways contributing to CE, subsequent description potential targeted therapies. There discussion identified cellular/cytotoxic contributors as well mechanisms that influence blood-brain-barrier (BBB) disruption/vasogenic edema, caveat this distinction may be somewhat artificial since molecular processes these interrelated. While exhaustive all putative contributions beyond scope review, roles some key highlighted, references provided for further details. Potential future targets treating presented based mechanisms. We thus aim provide translational synopsis present strategies targeting after TBI context paradigm shift towards precision medicine. article part Special Issue entitled "Novel Treatments Traumatic Brain Injury".

Язык: Английский

Процитировано

370
The anatomy and immunology of vasculature in the central nervous system DOI Open Access
Panagiotis Mastorakos, Dorian B. McGavern

Science Immunology, Год журнала: 2019, Номер 4(37)

Опубликована: Июль 5, 2019

Barriers between circulation and the central nervous system (CNS) play a key role in development modulation of CNS immune responses. Structural variations vasculature traversing different anatomical regions within strongly influence where how responses first develop. Here, we provide an overview cerebrovascular anatomy, focusing on blood-CNS interface steady-state immunology compartment. We then discuss is affected by influences pathophysiological states, such as autoimmune disease, injury, cerebral ischemia, infection.

Язык: Английский

Процитировано

250
Microglia and macrophage metabolism in CNS injury and disease: The role of immunometabolism in neurodegeneration and neurotrauma DOI Creative Commons
Nicholas A. Devanney, Andrew N. Stewart,

John C. Gensel

и другие.

Experimental Neurology, Год журнала: 2020, Номер 329, С. 113310 - 113310

Опубликована: Апрель 11, 2020

Innate immune responses, particularly activation of macrophages and microglia, are increasingly implicated in CNS disorders. It is now appreciated that the heterogeneity functions adopted by these cells dictates neuropathophysiology. Research efforts to characterize range pro-inflammatory anti-inflammatory phenotypes microglia fueled potential for inflammatory both exacerbate neurodegeneration promote repair/disease resolution. The stimulation-based, M1/M2 classification system has emerged over last decade as a common language discuss macrophage across different fields. However, discontinuities between phenotypic markers function create hurdles utility development effective immunomodulatory therapeutics neuroinflammation. A framework approach from function-based comes rapidly emerging evidence metabolic processes regulate cell activation. This concept immunometabolism, however, only beginning unfold study yet receive much focus context neurotrauma. In this review, we first current views limitations neuropathological studies. We then review literature supporting metabolism regulator vitro. Lastly, evaluate regulates phenotype vivo models Alzheimer's disease (AD), stroke, traumatic brain injury (TBI) spinal cord (SCI).

Язык: Английский

Процитировано

227
Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury DOI Creative Commons
Haijian Wu, Jingwei Zheng, Shenbin Xu

и другие.

Journal of Neuroinflammation, Год журнала: 2021, Номер 18(1)

Опубликована: Янв. 5, 2021

Abstract Background Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial/macrophage activation neuroinflammation are key cellular events following TBI, but the regulatory functional mechanisms still not well understood. Myeloid-epithelial-reproductive tyrosine kinase (Mer), member Tyro-Axl-Mer (TAM) family receptor kinases, regulates multiple features microglial/macrophage physiology. However, its function in regulating innate immune response M1/M2 polarization TBI has been addressed. The present study aimed to evaluate role Mer TBI. Methods controlled cortical impact (CCI) mouse model was employed. siRNA intracerebroventricularly administered, recombinant protein S (PS) intravenously applied for intervention. neurobehavioral assessments, RT-PCR, Western blot, magnetic-activated cell sorting, immunohistochemistry confocal microscopy analysis, Nissl Fluoro-Jade B staining, water content measurement, contusion volume assessment were performed. Results upregulated acute stage Mechanistically, activates signal transducer activator transcription 1 (STAT1)/suppressor cytokine signaling 1/3 (SOCS1/3) pathway. Inhibition markedly decreases M2-like while increases M1-like polarization, which exacerbates secondary damage sensorimotor deficits after Recombinant PS exerts beneficial effects mice through activation. Conclusions an important regulator neuroinflammation, may be considered as potential target therapeutic intervention

Язык: Английский

Процитировано

218
MicroRNAs in Neuroinflammation: Implications in Disease Pathogenesis, Biomarker Discovery and Therapeutic Applications DOI Creative Commons
Jessy A. Slota, Stephanie A. Booth

Non-Coding RNA, Год журнала: 2019, Номер 5(2), С. 35 - 35

Опубликована: Апрель 24, 2019

The central nervous system can respond to threat via the induction of an inflammatory response. Under normal circumstances this response is tightly controlled, however uncontrolled neuroinflammation a hallmark many neurological disorders. MicroRNAs are small non-coding RNA molecules that important for regulating cellular processes. ability microRNAs modulate signaling area ongoing research, which has gained much attention in recent years. may either promote or restrict signaling, and exacerbate ameliorate pathological consequences excessive neuroinflammation. aim review summarize mode regulation several well-studied context neuroinflammation, including miR-155, miR-146a, miR-124, miR-21 let-7. Furthermore, miRNA deregulation during disorders feature discussed, Multiple Sclerosis, Alzheimer's disease, Parkinson's Prion diseases, Japanese encephalitis, Herpes ischemic stroke traumatic brain injury. There also been considerable interest use altered microRNA signatures as biomarkers these expression even serve basis future therapeutic strategies help treat

Язык: Английский

Процитировано

199
Treatment targets for M2 microglia polarization in ischemic stroke DOI
Ji Wang,

Hongyi Xing,

Lin Wan

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2018, Номер 105, С. 518 - 525

Опубликована: Июнь 6, 2018

Язык: Английский

Процитировано

194
A new neutrophil subset promotes CNS neuron survival and axon regeneration DOI

Andrew Sas,

Kevin Carbajal,

Andrew Jerome

и другие.

Nature Immunology, Год журнала: 2020, Номер 21(12), С. 1496 - 1505

Опубликована: Окт. 26, 2020

Язык: Английский

Процитировано

194
Current understanding of neuroinflammation after traumatic brain injury and cell-based therapeutic opportunities DOI Creative Commons
Ye Xiong, Asim Mahmood, Michael Chopp

и другие.

Chinese Journal of Traumatology, Год журнала: 2018, Номер 21(3), С. 137 - 151

Опубликована: Апрель 24, 2018

Traumatic brain injury (TBI) remains a major cause of death and disability worldwide. Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer's disease, Parkinson's chronic traumatic encephalopathy. Despite improved supportive rehabilitative care patients, unfortunately, all late phase clinical trials in have yet to yield safe effective neuroprotective treatment. The disappointing may be attributed variability treatment approaches heterogeneity the population patients as well race against time prevent or reduce inexorable cell death. not just acute event but disease. Among many mechanisms involved secondary after TBI, emerging preclinical studies indicate posttraumatic prolonged progressive neuroinflammation associated with neurodegeneration which treatable long initiating injury. This review provides overview recent understanding cell-based therapies target promote functional recovery TBI.

Язык: Английский

Процитировано

188
Neurosteroids as regulators of neuroinflammation DOI Creative Commons
Canelif Yılmaz, Kanelina Karali,

Georgia Fodelianaki

и другие.

Frontiers in Neuroendocrinology, Год журнала: 2019, Номер 55, С. 100788 - 100788

Опубликована: Сен. 9, 2019

Neuroinflammation is a physiological protective response in the context of infection and injury. However, neuroinflammation, especially if chronic, may also drive neurodegeneration. Neurodegenerative diseases, such as multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's (PD) traumatic brain injury (TBI), display inflammatory activation microglia astrocytes. Intriguingly, central nervous system (CNS) highly steroidogenic environment synthesizing steroids de novo, well metabolizing deriving from circulation. Neurosteroid synthesis can be substantially affected by while, turn, several steroids, 17β-estradiol, dehydroepiandrosterone (DHEA) allopregnanolone, regulate neuroinflammatory responses. Here, we review role neurosteroids neuroinflammation MS, AD, PD TBI describe underlying molecular mechanisms. Moreover, introduce concept that synthetic neurosteroid analogues could potentially utilized for treatment neurodegenerative diseases future.

Язык: Английский

Процитировано

182