Intersecting Pathways: The Role of Metabolic Dysregulation, Gastrointestinal Microbiome, and Inflammation in Acute Ischemic Stroke Pathogenesis and Outcomes DOI Open Access
Jarosław Nuszkiewicz,

Beata Kukulska-Pawluczuk,

Katarzyna Piec

и другие.

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(14), С. 4258 - 4258

Опубликована: Июль 21, 2024

Acute ischemic stroke (AIS) remains a major cause of mortality and long-term disability worldwide, driven by complex multifaceted etiological factors. Metabolic dysregulation, gastrointestinal microbiome alterations, systemic inflammation are emerging as significant contributors to AIS pathogenesis. This review addresses the critical need understand how these factors interact influence risk outcomes. We aim elucidate roles dysregulated adipokines in obesity, impact gut microbiota disruptions, neuroinflammatory cascade initiated lipopolysaccharides (LPS) AIS. Dysregulated obesity exacerbate inflammatory responses, increasing severity. Disruptions subsequent LPS-induced neuroinflammation further link Advances neuroimaging biomarker development have improved diagnostic precision. Here, we highlight for approach management, integrating metabolic, microbiota, insights. Potential therapeutic strategies targeting pathways could significantly improve prevention treatment. Future research should focus on elucidating developing targeted interventions mitigate impacts metabolic imbalances,

Язык: Английский

Deplete and repeat: microglial CSF1R inhibition and traumatic brain injury DOI Creative Commons

Rebecca Boland,

Olga N. Kokiko‐Cochran

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Фев. 21, 2024

Traumatic brain injury (TBI) is a public health burden affecting millions of people. Sustained neuroinflammation after TBI often associated with poor outcome. As result, increased attention has been placed on the role immune cells in post-injury recovery. Microglia are highly dynamic and play key neuroinflammatory response. Therefore, microglia represent malleable target that could substantially influence long-term outcome TBI. This review highlights cell specific pathophysiology. have manipulated via genetic deletion, drug inhibition, pharmacological depletion various pre-clinical models. Notably, colony stimulating factor 1 (CSF1) its receptor (CSF1R) gained much traction recent years as microglia. CSF1R transmembrane tyrosine kinase essential for proliferation, differentiation, survival. Small molecule inhibitors targeting result swift effective rodents. Moreover, discontinuation sufficient repopulation. Attention summarizing studies incorporate inhibition Indeed, affects multiple aspects pathophysiology, including neuroinflammation, oxidative stress, functional recovery measurable astrocytes, peripheral cells, neurons. Taken together, data highlight an important sustaining increasing risk which lends to neuronal damage behavioral deficits chronically Ultimately, insights from critical understanding temporospatial develop mediating pathophysiology

Язык: Английский

Процитировано

8
Immune mechanisms and shared immune targets in neurodegenerative diseases DOI
Howard L. Weiner

Nature Reviews Neurology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

Язык: Английский

Процитировано

8
Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice DOI Creative Commons
Wei Wei, Seyed Siyawasch Justus Lattau, Wenqiang Xin

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

Abstract Microglia are critically involved in post‐stroke inflammation affecting neurological outcomes. Lipid droplet (LD) accumulation microglia results a dysfunctional and pro‐inflammatory state the aged brain worsens outcome of neuroinflammatory neurodegenerative diseases. However, role LD‐rich (LDRM) under stroke conditions is unknown. Using vitro vivo models, herein patterns microglial LD their corresponding inflammatory signaling cascades studied. Interactions between temporal spatial dynamics lipid profiles phenotypes different regions found. Hence, display enhanced levels elevated perilipin 2 (PLIN2) expression when exposed to hypoxia or stroke. Such LDRM exhibit high TNF‐α, IL‐6, IL‐1β as well phenotype differentially expressed metabolism‐related genes. These post‐ischemic alterations result distinct with dynamics, especially regard cholesteryl ester triacylglycerol levels, further exacerbating inflammation. The present study sheds new light on dynamic changes aggregation ischemia, demonstrating mutual mechanism function, which contributes progression injury.

Язык: Английский

Процитировано

7
Magnetic susceptibility of the hippocampal subfields and basal ganglia in acute mild traumatic brain injury DOI Creative Commons
C. Essex, Mayan J. Bedggood, Jenna L. Merenstein

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Abstract Despite vulnerability to microstructural tissue damage following mild traumatic brain injury (mTBI), key subcortical regions have been overlooked in quantitative susceptibility mapping (QSM) studies. Alterations composition the functionally and structurally distinct hippocampal subfields basal ganglia may reflect symptomatology, better characterisation of these is needed in-crease our understanding mTBI pathophysiology. To address this issue, we used magnetic source-separated QSM quantify spatial distributions positive (iron-related) negative (myelin-, protein-, calcium-related) across 10 substructures 16 segmentations 25 male participants with acute (< 14 days) sports-related (sr-mTBI). Additional variables interest including age, severity, days since at time resonance imaging (MRI) scan were also correlated both values. Primary analyses indicated no significant difference values between sr-mTBI controls for ROIs. For sign values, was significantly less cornu ammonis 4 (CA4) region only ( p FDR < 0.05). In line known linear relationship iron deposition age deep grey matter sites, particularly within first three decades life, relationships observed putamen, caudate, red nucleus, parabrachial pigmented ventral pallidum Positive absolute fimbria, extended amygdala 0.05), suggesting age-related calcifications regions. A indicating potential changes myelin content region. No associations be-tween any other variable signed The results study contribute to, extend, prior literature regarding temporal kinetics biomagnetic substrates as a function ageing. Decreased after CA4 suggests injury-related effects on or cell loss; interesting finding light well-established pathology chronic encephalopathy (CTE). lack between-group differences suggest that alterations not be quantifiable stage ROIs masked by common feature all young cohort. Future research should consider use longitudinal designs mitigate influence factors.

Язык: Английский

Процитировано

1
Single‐cell RNA‐sequencing analysis reveals enhanced non‐canonical neurotrophic factor signaling in the subacute phase of traumatic brain injury DOI Creative Commons
Xuecheng Qiu,

Yaling Guo,

M Liu

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 29(11), С. 3446 - 3459

Опубликована: Июнь 2, 2023

Traumatic brain injury (TBI) is a leading cause of long-term disability in young adults and induces complex neuropathological processes. Cellular autonomous intercellular changes during the subacute phase contribute substantially to neuropathology TBI. However, underlying mechanisms remain elusive. In this study, we explored dysregulated cellular signaling TBI.Single-cell RNA-sequencing data (GSE160763) TBI were analyzed explore cell-cell communication Upregulated neurotrophic factor was validated mouse model Primary cell cultures lines used as vitro models examine potential affecting signaling.Single-cell analysis revealed that microglia astrocytes most affected cells Cell-cell demonstrated mediated by non-canonical factors midkine (MDK), pleiotrophin (PTN), prosaposin (PSAP) microglia/astrocytes upregulated Time-course profiling showed MDK, PTN, PSAP expression primarily TBI, major source MDK PTN after studies enhanced activated microglia. Moreover, promoted proliferation neural progenitors derived from human-induced pluripotent stem (iPSCs) neurite growth iPSC-derived neurons, whereas exclusively stimulated growth.The played crucial role neuroregeneration.

Язык: Английский

Процитировано

14
Integrating Bulk RNA and Single-Cell Sequencing Data Unveils Efferocytosis Patterns and ceRNA Network in Ischemic Stroke DOI
Jing Yuan,

Yu-sha Liao,

Tie-chun Zhang

и другие.

Translational Stroke Research, Год журнала: 2024, Номер unknown

Опубликована: Апрель 28, 2024

Язык: Английский

Процитировано

6
The Gut-Brain Axis and Neuroinflammation in Traumatic Brain Injury DOI
Mega Obukohwo Oyovwi, Onoriode Andrew Udi

Molecular Neurobiology, Год журнала: 2024, Номер 62(4), С. 4576 - 4590

Опубликована: Окт. 28, 2024

Язык: Английский

Процитировано

6
Microglia dynamic response and phenotype heterogeneity in neural regeneration following hypoxic-ischemic brain injury DOI Creative Commons

Hongxin Quan,

Runrui Zhang

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 29, 2023

Hypoxic-ischemic brain injury poses a significant threat to the neural niche within central nervous system. In response this pathological process, microglia, as innate immune cells in system, undergo rapid morphological, molecular and functional changes. Here, we comprehensively review these dynamic changes microglial hypoxic-ischemic under conditions, including stroke, chronic intermittent hypoxia neonatal injury. We focus on regulation of signaling pathways further describe process microenvironment remodeling tissue regeneration mediated by microglia after

Язык: Английский

Процитировано

13
The dual role of microglia in intracerebral hemorrhage DOI
Yue Sun,

Wentao Sun,

Jiawei Liu

и другие.

Behavioural Brain Research, Год журнала: 2024, Номер 473, С. 115198 - 115198

Опубликована: Авг. 10, 2024

Язык: Английский

Процитировано

5
The cell‐specific roles of Nrf2 in acute and chronic phases of ischemic stroke DOI Creative Commons

George Fadoul,

Miloš D. Ikonomović, Feng Zhang

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 30(3)

Опубликована: Сен. 16, 2023

Abstract Ischemic stroke refers to the sudden loss of blood flow in a specific area brain. It is fifth leading cause mortality and permanent disability. The transcription factor nuclear erythroid 2‐related 2 (Nrf2) controls production several antioxidants protective proteins it has been investigated as possible pharmaceutical target for reducing harmful oxidative events brain ischemia. Each cell type exhibits different roles behaviors phases post‐stroke, which comprehensive yet important understand optimize management strategies goals care patients. In this review, we comprehensively summarize effects Nrf2 experimental ischemic stroke, emphasizing role types including neurons, astrocytes, oligodendrocytes, microglia, endothelial cells during acute chronic providing insights on neuroprotective each throughout long term care. We also highlight importance targeting clinical settings while considering variety factors such age, drug dosage, delivery route, time administration.

Язык: Английский

Процитировано

11