The role of peripheral inflammatory insults in Alzheimer’s disease: a review and research roadmap DOI Creative Commons
Keenan A. Walker, Lydia M. Le Page, Niccolò Terrando

et al.

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: June 5, 2023

Abstract Peripheral inflammation, defined as inflammation that occurs outside the central nervous system, is an age-related phenomenon has been identified a risk factor for Alzheimer’s disease. While role of chronic peripheral well characterized in context dementia and other conditions, less known about neurologic contribution acute inflammatory insults take place system. Herein, we define immune challenge form pathogen exposure (e.g., viral infection) or tissue damage surgery) causes large, yet time-limited, response. We provide overview clinical translational research examined connection between disease, focusing on three categories have received considerable attention recent years: infection, critical illness, surgery. Additionally, review neurobiological mechanisms which facilitate neural response to discuss potential blood–brain barrier components neuro-immune axis After highlighting knowledge gaps this area research, propose roadmap address methodological challenges, suboptimal study design, paucity transdisciplinary efforts thus far limited our understanding how pathogen- damage-mediated may contribute Finally, therapeutic approaches designed promote resolution be used following preserve brain health limit progression neurodegenerative pathology.

Language: Английский

The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology DOI Creative Commons

Andrina Rutsch,

Johan B. Kantsjö,

Francesca Ronchi

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 10, 2020

The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is condition associated not only with gastrointestinal disorders but diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect central nervous system (CNS) inflammation. tract are communicating through bidirectional network of signaling pathways called gut-brain axis, which consists multiple connections, including vagus nerve, immune system, bacterial metabolites products. During these dysregulated altered permeability blood-brain barrier (BBB) neuroinflammation. However, numerous mechanisms behind impact gut neuro-development -pathogenesis remain poorly understood. There several involved CNS homeostasis Among those, inflammasome pathway been linked to neuroinflammatory conditions such sclerosis, Alzheimer’s Parkinson’s diseases, anxiety depressive-like disorders. complex assembles upon cell activation due exposure microbes, danger signals, or stress lead production pro-inflammatory cytokines (interleukin-1β interleukin-18) pyroptosis. Evidences suggest there reciprocal influence brain. how this precisely working yet be discovered. Herein, we discuss status knowledge open questions field focusing on function products cells during healthy inflammatory conditions, neuropsychiatric In particular, focus innate mechanism certain microbes.

Language: Английский

Citations

567
Signaling inflammation across the gut-brain axis DOI
Gulistan Agirman, Kristie B. Yu, Elaine Y. Hsiao

et al.

Science, Journal Year: 2021, Volume and Issue: 374(6571), P. 1087 - 1092

Published: Nov. 25, 2021

The brain and gastrointestinal tract are critical sensory organs responsible for detecting, relaying, integrating, responding to signals derived from the internal external environment. At interface of this function, immune cells in intestines consistently survey environmental factors, eliciting responses that inform on physiological state body. Recent research reveals cross-talk along gut-brain axis regulates inflammatory nociception, responses, homeostasis. Here, we discuss molecular cellular mechanisms involved signaling inflammation across axis. We further highlight interactions between gut inflammation-associated diseases.

Language: Английский

Citations

478
Functional characterization of the dural sinuses as a neuroimmune interface DOI
Justin Rustenhoven, Antoine Drieu, Tornike Mamuladze

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(4), P. 1000 - 1016.e27

Published: Jan. 27, 2021

Language: Английский

Citations

458
Revisiting the neurovascular unit DOI

Samantha Schaeffer,

Costantino Iadecola

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(9), P. 1198 - 1209

Published: Aug. 5, 2021

Language: Английский

Citations

427
Fluid transport in the brain DOI
Martin Kaag Rasmussen, Humberto Mestre, Maiken Nedergaard

et al.

Physiological Reviews, Journal Year: 2021, Volume and Issue: 102(2), P. 1025 - 1151

Published: May 5, 2021

The brain harbors a unique ability to, figuratively speaking, shift its gears. During wakefulness, the is geared fully toward processing information and behaving, while homeostatic functions predominate during sleep. blood-brain barrier establishes stable environment that optimal for neuronal function, yet imposes physiological problem; transcapillary filtration forms extracellular fluid in other organs reduced to minimum brain. Consequently, depends on special [the cerebrospinal (CSF)] flushed into along perivascular spaces created by astrocytic vascular endfeet. We describe this pathway, coined term glymphatic system, based dependency endfeet their adluminal expression of aquaporin-4 water channels facing CSF-filled spaces. Glymphatic clearance potentially harmful metabolic or protein waste products, such as amyloid-β, primarily active sleep, when drivers, cardiac cycle, respiration, slow vasomotion, together efficiently propel CSF inflow periarterial brain's space contains an abundance proteoglycans hyaluronan, which provide low-resistance hydraulic conduit rapidly can expand shrink sleep-wake cycle. system brain, meets requisites maintain homeostasis similar peripheral organs, considering blood-brain-barrier paths formation egress CSF.

Language: Английский

Citations

331
Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders DOI Open Access
Simone Brioschi, Wei-Le Wang, Vincent Peng

et al.

Science, Journal Year: 2021, Volume and Issue: 373(6553)

Published: June 3, 2021

The meninges contain adaptive immune cells that provide immunosurveillance of the central nervous system (CNS). These are thought to derive from systemic circulation. Through single-cell analyses, confocal imaging, bone marrow chimeras, and parabiosis experiments, we show meningeal B locally calvaria, which harbors a niche for hematopoiesis. reach calvaria through specialized vascular connections. This calvarial-meningeal path cell development may CNS with constant supply educated by antigens. Conversely, subset antigen-experienced populate in aging mice blood-borne. results identify private source cells, help maintain privilege within CNS.

Language: Английский

Citations

327
Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons DOI
Kalil Alves de Lima, Justin Rustenhoven, Sandro Dá Mesquita

et al.

Nature Immunology, Journal Year: 2020, Volume and Issue: 21(11), P. 1421 - 1429

Published: Sept. 14, 2020

Language: Английский

Citations

300
Neuromodulation by the immune system: a focus on cytokines DOI
Andrea Francesca Salvador, Kalil Alves de Lima, Jonathan Kipnis

et al.

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(8), P. 526 - 541

Published: March 1, 2021

Language: Английский

Citations

276
Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis DOI Creative Commons
Ashley C. Bolte, Arun B. Dutta,

Mariah E. Hurt

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Sept. 10, 2020

Abstract Traumatic brain injury (TBI) is a leading global cause of death and disability. Here we demonstrate in an experimental mouse model TBI that mild forms trauma severe deficits meningeal lymphatic drainage begin within hours last out to at least one month post-injury. To investigate mechanism underlying impaired function TBI, examined how increased intracranial pressure (ICP) influences the lymphatics. We ICP can contribute dysfunction. Moreover, show pre-existing dysfunction before leads neuroinflammation negative cognitive outcomes. Finally, report rejuvenation aged mice ameliorate TBI-induced gliosis. These findings provide insights into both causes consequences suggest therapeutics targeting system may offer strategies treat TBI.

Language: Английский

Citations

245
Molecular and spatial signatures of mouse brain aging at single-cell resolution DOI Creative Commons
William E. Allen, Timothy R. Blosser, Zuri A. Sullivan

et al.

Cell, Journal Year: 2022, Volume and Issue: 186(1), P. 194 - 208.e18

Published: Dec. 28, 2022

The diversity and complex organization of cells in the brain have hindered systematic characterization age-related changes its cellular molecular architecture, limiting our ability to understand mechanisms underlying functional decline during aging. Here, we generated a high-resolution cell atlas aging within frontal cortex striatum using spatially resolved single-cell transcriptomics quantified gene expression spatial major types these regions over mouse lifespan. We observed substantially more pronounced state, expression, non-neuronal neurons. Our data revealed signatures glial immune activation aging, particularly enriched subcortical white matter, identified both similarities notable differences cell-activation patterns induced by systemic inflammatory challenge. These results provide critical insights into inflammation brain.

Language: Английский

Citations

239