Neuroinflammation, Stroke, Blood-Brain Barrier Dysfunction, and Imaging Modalities

Stroke, Journal Year: 2022, Volume and Issue: 53(5), P. 1473 - 1486

Published: April 7, 2022

Maintaining blood-brain barrier (BBB) integrity is crucial for the homeostasis of central nervous system. Structurally comprising BBB, brain endothelial cells interact with pericytes, astrocytes, neurons, microglia, and perivascular macrophages in neurovascular unit. Brain ischemia unleashes a profound neuroinflammatory response to remove damaged tissue prepare repair. However, intense neuroinflammation occurring during acute phase stroke associated BBB breakdown, neuronal injury, worse neurological outcomes. Here, we critically discuss role ischemic pathology, focusing on interactions between system peripheral immune responses. We highlight inflammation-driven injury mechanisms stroke, including oxidative stress, increased MMP (matrix metalloproteinase) production, microglial activation, infiltration into tissue. provide an updated overview imaging techniques vivo detection permeability, leukocyte infiltration, upregulation cell adhesion molecules following injury. possibility clinical implementation modalities assess stroke-associated potential image-guided diagnosis treatment. summarize results from several studies evaluating efficacy anti-inflammatory interventions stroke. Although convincing preclinical evidence suggests that promising target thus far, translating these setting has proved difficult. Due dual inflammation progression damage, more research needed mechanistically understand when begins transition This could have important implications treatment by informing time- context-specific therapeutic interventions.

Language: Английский

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What is a cell type and how to define it?

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2739 - 2755

Published: July 1, 2022

Language: Английский

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A single-cell atlas of the normal and malformed human brain vasculature

Science, Journal Year: 2022, Volume and Issue: 375(6584)

Published: Jan. 27, 2022

Cerebrovascular diseases are a leading cause of death and neurologic disability. Further understanding disease mechanisms therapeutic strategies requires deeper knowledge cerebrovascular cells in humans. We profiled transcriptomes 181,388 to define cell atlas the adult human cerebrovasculature, including endothelial molecular signatures with arteriovenous segmentation expanded perivascular diversity. By leveraging this reference, we investigated cellular perturbations brain malformations, which stroke young people, identified pathologic transformations abnormal vascular patterning ontology vascularly derived inflammation. illustrate interplay between immune that contributes hemorrhage catalog opportunities for targeting angiogenic inflammatory programs malformations.

Language: Английский

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The neuroimmune axis of Alzheimer’s disease

Genome Medicine, Journal Year: 2023, Volume and Issue: 15(1)

Published: Jan. 26, 2023

Abstract Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder with multifaceted neuropathological features, including β-amyloid plaques, neurofibrillary tangles, neuroinflammation. Over the past decade, emerging evidence has implicated both beneficial pathological roles for innate immune genes cells, peripheral cells such as T which can infiltrate brain either ameliorate or exacerbate AD neuropathogenesis. These findings support neuroimmune axis of AD, in interplay adaptive systems inside outside critically impacts etiology pathogenesis AD. In this review, we discuss complexities neuropathology at levels genetics cellular physiology, highlighting signaling pathways associated risk interactions among brain. We emphasize role mechanisms by monocytes, influence neuropathology, microglial clearance amyloid-β peptide, key component plaque cores, pro-inflammatory cytotoxic activity microglia, astrogliosis, their vasculature. Finally, review challenges outlook establishing immune-based therapies treating preventing

Language: Английский

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Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke

Current Neurology and Neuroscience Reports, Journal Year: 2023, Volume and Issue: 23(8), P. 407 - 431

Published: July 3, 2023

Language: Английский

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Systemic inflammation after stroke: implications for post‐stroke comorbidities

EMBO Molecular Medicine, Journal Year: 2022, Volume and Issue: 14(9)

Published: Aug. 15, 2022

Language: Английский

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Hypertension, Neurovascular Dysfunction, and Cognitive Impairment

Hypertension, Journal Year: 2022, Volume and Issue: 80(1), P. 22 - 34

Published: Oct. 5, 2022

Hypertension affects a significant proportion of the adult and aging population represents an important risk factor for vascular cognitive impairment late-life dementia. Chronic high blood pressure continuously challenges structural functional integrity cerebral vasculature, leading to microvascular rarefaction dysfunction, neurovascular uncoupling that typically impairs supply. disrupts blood-brain barrier integrity, promotes neuroinflammation, may contribute amyloid deposition Alzheimer pathology. The mechanisms underlying these harmful effects are still focus investigation, but studies in animal models have provided molecular cellular mechanistic insights. Remaining questions relate whether adequate treatment hypertension prevent deterioration function, threshold treatment, most effective antihypertensive drugs. Recent advances biology, advanced brain imaging, detection subtle behavioral phenotypes begun provide insights into critical issues. Importantly, parallel analysis parameters humans is feasible, making it possible foster translational advancements. In this review, we evaluation evidence available experimental examine progress made identify remaining gaps knowledge.

Language: Английский

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Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease

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

Published: July 11, 2023

Abstract Vascular cognitive impairment and dementia (VCID) is commonly caused by vascular injuries in cerebral large small vessels a key driver of age-related decline. Severe VCID includes post-stroke dementia, subcortical ischemic multi-infarct mixed dementia. While acknowledged as the second most common form after Alzheimer’s disease (AD) accounting for 20% cases, AD frequently coexist. In VCID, vessel (cSVD) often affects arterioles, capillaries, venules, where arteriolosclerosis amyloid angiopathy (CAA) are major pathologies. White matter hyperintensities, recent infarcts, lacunes presumed origin, enlarged perivascular space, microbleeds, brain atrophy neuroimaging hallmarks cSVD. The current primary approach to cSVD treatment control risk factors such hypertension, dyslipidemia, diabetes, smoking. However, causal therapeutic strategies have not been established partly due heterogeneous pathogenesis this review, we summarize pathophysiology discuss probable etiological pathways focusing on hypoperfusion/hypoxia, blood–brain barriers (BBB) dysregulation, fluid drainage disturbances, inflammation define potential diagnostic targets

Language: Английский

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Magnetic iron oxide nanoparticles for brain imaging and drug delivery

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 197, P. 114822 - 114822

Published: April 21, 2023

Central nervous system (CNS) disorders affect as many 1.5 billion people globally. The limited delivery of most imaging and therapeutic agents into the brain is a major challenge for treatment CNS disorders. With advent nanotechnologies, controlled drugs with nanoparticles holds great promise in overcoming blood-brain barrier (BBB) improving efficacy. In recent years, magnetic iron oxide (MIONPs) have stood out promising theranostic nanoplatform drug they possess unique physical properties biodegradable characteristics. this review, we summarize advances MIONP-based platforms diseases. We firstly introduce methods synthesis surface functionalization MIONPs emphasis on inclusion biocompatible polymers that allow addition tailored physicochemical properties. then discuss vivo applications using MIONPs. Finally, present perspective remaining challenges possible future directions systems.

Language: Английский

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Functional ultrasound localization microscopy reveals brain-wide neurovascular activity on a microscopic scale

Nature Methods, Journal Year: 2022, Volume and Issue: 19(8), P. 1004 - 1012

Published: Aug. 1, 2022

The advent of neuroimaging has increased our understanding brain function. While most brain-wide functional imaging modalities exploit neurovascular coupling to map activity at millimeter resolutions, the recording responses microscopic scale in mammals remains privilege invasive electrophysiological or optical approaches, but is mostly restricted either cortical surface vicinity implanted sensors. Ultrasound localization microscopy (ULM) achieved transcranial cerebrovascular flow, up micrometre scales, by localizing intravenously injected microbubbles; however, long acquisition time required detect microbubbles within vessels so far ULM application mainly microvasculature structural imaging. Here we show how can be modified quantify hyperemia dynamically during activation reaching a 6.5-µm spatial and 1-s temporal resolution deep regions rat brain.

Language: Английский

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