The Blood–Brain Barrier, Oxidative Stress, and Insulin Resistance DOI Creative Commons
William A. Banks, Elizabeth M. Rhea

Antioxidants, Journal Year: 2021, Volume and Issue: 10(11), P. 1695 - 1695

Published: Oct. 27, 2021

The blood–brain barrier (BBB) is a network of specialized endothelial cells that regulates substrate entry into the central nervous system (CNS). Acting as interface between periphery and CNS, BBB must be equipped to defend against oxidative stress other free radicals generated in protect CNS. There are unique features brain increase susceptibility these stress. Insulin signaling can impacted by varying levels stress, with low being necessary for higher detrimental. cross order access which important peripheral metabolism well cognition. Any alterations transport due at could have downstream disease implications. In this review, we cover interactions BBB, how insulin related impact two diseases greatly affected resistance: diabetes mellitus Alzheimer’s disease.

Language: Английский

The blood-brain barrier in aging and neurodegeneration DOI Creative Commons
Emily G. Knox, María R. Aburto, Gerard Clarke

et al.

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(6), P. 2659 - 2673

Published: March 31, 2022

Abstract The blood-brain barrier (BBB) is vital for maintaining brain homeostasis by enabling an exquisite control of exchange compounds between the blood and parenchyma. Moreover, BBB prevents unwanted toxins pathogens from entering brain. This barrier, however, breaks down with age further disruption a hallmark many age-related disorders. Several drugs have been explored, thus far, to protect or restore function. With recent connection gut microbiota, microbial-derived metabolites explored their capabilities physiology. review, will focus on components that make up BBB, dissect levels discuss current therapeutics maintain integrity discoveries effects

Language: Английский

Citations

380
The blood–brain barrier in systemic infection and inflammation DOI Creative Commons
Ian Galea

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 18(11), P. 2489 - 2501

Published: Sept. 30, 2021

Abstract The vascular blood–brain barrier is a highly regulated interface between the blood and brain. Its primary function to protect central neurons while signaling presence of systemic inflammation infection brain enable protective sickness behavior response. With increasing degrees duration inflammation, becomes more permeable solutes, undergoes an increase in lymphocyte trafficking, infiltrated by innate immune cells; endothelial cell damage may occasionally occur. Perturbation neuronal results clinical features encephalopathy. Here, molecular cellular anatomy reviewed, first healthy context second inflammatory context. Distinct from mediators barrier’s response several moderators influence direction magnitude at genetic, system, levels. These include sex, genetic background, age, pre-existing pathology, comorbidity, gut dysbiosis. Further progress required define measure order explain heterogeneity observed animal human studies.

Language: Английский

Citations

375
Blood–Brain Barrier Breakdown: An Emerging Biomarker of Cognitive Impairment in Normal Aging and Dementia DOI Creative Commons
Basharat Hussain, Cheng Fang, Junlei Chang

et al.

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Aug. 19, 2021

The blood-brain barrier (BBB) plays a vital role in maintaining the specialized microenvironment of neural tissue. It separates peripheral circulatory system from brain parenchyma while facilitating communication. Alterations distinct physiological properties BBB lead to breakdown associated with normal aging and various neurodegenerative diseases. In this review, we first briefly discuss process, then review phenotypes mechanisms that further cause neurodegeneration cognitive impairments. We also summarize dementia such as Alzheimer's disease (AD) vascular (VaD) subsequently disruption correlated cognition decline. Overlaps between AD VaD are discussed. Techniques could identify biomarkers summarized. Finally, concluded be used an emerging biomarker assist diagnose impairment dementia.

Language: Английский

Citations

186
The neuroimmune axis of Alzheimer’s disease DOI Creative Commons
Mehdi Jorfi,

Anna Maaser-Hecker,

Rudolph E. Tanzi

et al.

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

Citations

170
Postoperative delirium and changes in the blood–brain barrier, neuroinflammation, and cerebrospinal fluid lactate: a prospective cohort study DOI Creative Commons
Jennifer Taylor,

Margaret Parker,

Cameron Casey

et al.

British Journal of Anaesthesia, Journal Year: 2022, Volume and Issue: 129(2), P. 219 - 230

Published: Feb. 8, 2022

Language: Английский

Citations

113
APOE4 derived from astrocytes leads to blood–brain barrier impairment DOI Creative Commons
Rosemary J. Jackson,

Jonah C Meltzer,

Huong Nguyen

et al.

Brain, Journal Year: 2021, Volume and Issue: 145(10), P. 3582 - 3593

Published: Dec. 23, 2021

Abstract Apolipoprotein E (ApoE) is a multifaceted secreted molecule synthesized in the CNS by astrocytes and microglia, periphery largely liver. ApoE has been shown to impact integrity of blood–brain barrier, and, humans, APOE4 allele gene reported lead leaky barrier. We used specific knock-in mice expressing each common (human) alleles, longitudinal multiphoton intravital microscopy, directly monitor various isoforms on barrier integrity. found that humanized APOE4, but not APOE2 or APOE3, show increased MMP9, impaired tight junctions, reduced astrocyte end-foot coverage blood vessels. Removal astrocyte-produced ApoE4 led amelioration all phenotypes while removal ApoE3 had no effect This work shows cell gain function dysfunction BBB implicates production ApoE4, possibly as astrocytic end foot interactions with vessels, key regulator

Language: Английский

Citations

104
Implications of Gut Microbiota in Neurodegenerative Diseases DOI Creative Commons
Haoming Zhang, Yijia Chen, Zifan Wang

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 14, 2022

The morbidity associated with neurodegenerative diseases (NDs) is increasing, posing a threat to the mental and physical quality of life humans. crucial effect microbiota on brain physiological processes mediated through bidirectional interaction, termed as gut–brain axis (GBA), which being investigated in studies. Many clinical laboratory trials have indicated importance development NDs via various microbial molecules that transmit from gut across GBA or nervous system. In this review, we summarize implications ND, will be beneficial for understanding etiology progression may turn help developing ND interventions treatments these diseases.

Language: Английский

Citations

102
Blood–brain barrier link to human cognitive impairment and Alzheimer’s disease DOI
Giuseppe Barisano, Axel Montagne, Kassandra Kisler

et al.

Nature Cardiovascular Research, Journal Year: 2022, Volume and Issue: 1(2), P. 108 - 115

Published: Feb. 7, 2022

Language: Английский

Citations

94
Role of Reactive Oxygen Species in Aging and Age-Related Diseases: A Review DOI
Muzahidul I. Anik, Niaz Mahmud, Abdullah Al Masud

et al.

ACS Applied Bio Materials, Journal Year: 2022, Volume and Issue: 5(9), P. 4028 - 4054

Published: Aug. 31, 2022

Research on the role of reactive oxygen species (ROS) in aging process has advanced significantly over last two decades. In light recent findings, ROS takes part cells along with contributing to various physiological signaling pathways. Antioxidants being cells' natural defense mechanism against ROS-mediated alteration, play an imperative maintain intracellular homeostasis. Although complete understanding regulated is yet be fully comprehended, current insights into sources cellular and their correlation age-related diseases are portrayed this review. addition, results effect antioxidants homeostasis as well advances clinical trials also discussed detail. The future perspective ROS-antioxidant dynamics antiaging research marshaled provide directions for fields.

Language: Английский

Citations

93
Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota–gut–brain axis DOI Creative Commons
María R. Aburto, John F. Cryan

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(4), P. 222 - 247

Published: Feb. 14, 2024

Crosstalk between gut and brain has long been appreciated in health disease, the microbiota is a key player communication these two distant organs. Yet, mechanisms through which influences development function of gut–brain axis remain largely unknown. Barriers present are specialized cellular interfaces that maintain strict homeostasis different compartments across this axis. These barriers include epithelial barrier, blood–brain barrier blood–cerebrospinal fluid barrier. ideally positioned to receive communicate microbial signals constituting gateway for gut–microbiota–brain communication. In Review, we focus on how modulation by can constitute an important channel Moreover, malfunction upon alterations composition could form basis various conditions, including often comorbid neurological gastrointestinal disorders. Thus, should unravelling molecular move from simplistic framing as 'leaky gut'. A mechanistic understanding barriers, especially during critical windows development, be aetiology The modulator This Review provides overview examines role disease.

Language: Английский

Citations

92