Downregulation of Notch Signaling‐Stimulated Genes in Neurovascular Unit Alterations Induced by Chronic Cerebral Hypoperfusion DOI Creative Commons

Dewen Ru,

Zengyu Zhang, Meng Liu

et al.

Immunity Inflammation and Disease, Journal Year: 2024, Volume and Issue: 12(11)

Published: Nov. 1, 2024

ABSTRACT Background Chronic cerebral hypoperfusion (CCH) is a key contributor to vascular cognitive impairment (VCI) and typically associated with blood–brain barrier (BBB) damage. This study investigates the pathological mechanisms underlying CCH‐induced neurovascular unit (NVU) alterations. Methods A mouse model of CCH was established using bilateral common carotid artery stenosis (BCAS) procedure. Decreased blood flow (CBF) impaired BBB integrity were assessed. Brain microvessel (BMV)‐specific transcriptome profiles analyzed RNA‐seq, supplemented published single‐cell RNA‐seq data. Results revealed neuroinflammation‐related gene activation significant downregulation Notch signaling pathway genes in BMVs post‐BCAS. Upregulated differentially expressed (DEGs) enriched microglia/macrophages, while downregulated DEGs prominent endothelial cells pericytes. Enhanced vascular‐associated microglia (VAM) linked Conclusion induces NVU changes, marked by microglia‐associated neuroinflammation downregulation. These insights highlight potential therapeutic targets for treating neuroinflammatory vascular‐related neurodegenerative diseases.

Language: Английский

Edaravone dexborneol alleviates ischemic injury and neuroinflammation by modulating microglial and astrocyte polarization while inhibiting leukocyte infiltration DOI Creative Commons
Dongxue Wang, Yutao Wang, Junfeng Shi

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 130, P. 111700 - 111700

Published: Feb. 20, 2024

Poststroke inflammation is essential in the mechanism of secondary injury, and it orchestrated by resident microglia, astrocytes, circulating immune cells. Edaravone dexborneol (EDB) a combination edaravone borneol that has been identified as clinical protectant for stroke management. In this study, we verified anti-inflammatory effect EDB mouse model ischemia investigated its modulatory action on inflammation-related C57BL/6 male mice, which had transient middle cerebral artery occlusion (tMCAO), were treated (i.p.) with (15 mg/kg). administration significantly reduced brain infarction improved sensorimotor function after stroke. And alleviated neuroinflammation restraining polarization microglia/macrophages astrocyte toward proinflammatory phenotype inhibiting production cytokines (such IL-1β, TNF-α, IL-6) chemokines (including MCP-1 CXCL1). Furthermore, ameliorated MCAO-induced impairment Blood-brain barrier (BBB) suppressing degradation tight junction protein attenuated accumulation peripheral leukocytes ischemic brain. Additionally, systemic inhibited macrophage phenotypic shift M1 macrophage-dependent inflammatory response spleen blood. Collectively, protects against injury activation astrocytes through reduction invasion cells, reduces central following

Language: Английский

Citations

15
Effects of edaravone dexborneol on functional outcome and inflammatory response in patients with acute ischemic stroke DOI Creative Commons
Wenxia Chen, Hanqing Zhang, Zhenzhen Li

et al.

BMC Neurology, Journal Year: 2024, Volume and Issue: 24(1)

Published: June 20, 2024

Abstract Background Edaravone dexborneol has been reported as an effective neuroprotective agent in the treatment of acute ischemic stroke (AIS). This study aimed at investigating impact edaravone on functional outcomes and systematic inflammatory response AIS patient. Methods All participants were recruited from AISRNA (registered 21/11/2019, NCT04175691 [ClinicalTrials.gov]) between January 2022 December 2022. The patients divided into two groups based whether they received (37.5 mg/12 hours, IV) within 48 h after onset. Inflammatory was determined by detecting levels cytokines (interleukin-2 [IL-2], IL-4, IL-5, IL-8, IL-6, IL-10, IL-12p70, IL-17, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], IFN-α, IL-1β) 14 days Results Eighty-five included study. Patients treated with showed a significantly higher proportion modified Rankin Scale score < 2 compared to those who did not receive this (70.7% versus 47.8%; P = 0.031). Furthermore, individuals receiving injection exhibited lower expression interleukin (IL)-1β, along IL-4 IL-10 during phase ( 0.05). These trends observed for IL-2, factor-α, IFN-α > Conclusions Treatment resulted favorable outcome 90 post-stroke onset when without intervention; it also suppressed proinflammatory factors while increasing anti-inflammatory levels. Trial registration ClinicalTrials.gov NCT04175691. Registered November 21, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691 .

Language: Английский

Citations

5
Early functional and structural hippocampal impairment in a bilateral common carotid artery stenosis mouse model DOI Creative Commons
Ping Tang, Yi Sun, Chun‐Sheng Yang

et al.

Animal Models and Experimental Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Abstract Background Subcortical ischemic vascular dementia (SIVD) is a common subtype of dementia. Currently, the bilateral carotid artery stenosis (BCAS) mouse model most suitable SIVD rodent model. In this study, we investigated functional and structural impairments in hippocampus 1 month after BCAS. Methods We used behavioral tests, laser speckle flowmetry, long‐term potentiation, histochemical staining, molecular experiments, voxel‐based morphometry to evaluate hippocampal impairments. Results Behavioral studies revealed that BCAS mice exhibited worse performance. Laser flowmetry detected an obvious decrease cerebral blood flow. The synaptic plasticity perforant path‐dentate gyrus pathway was inhibited. Decreased fractional anisotropy increased mean diffusivity were via diffusion tensor imaging data. A reduction gray matter volume, which prominent its surrounding areas, analysis. Impairments cell morphology myelin integrity validated using staining biology techniques. addition, numbers GFAP + astrocytes Iba1 microglia hippocampus. Conclusions Overall, our study demonstrates early contributing learning memory deficits BCAS, indicating vulnerable chronic ischemia.

Language: Английский

Citations

0
Salidroside attenuates cognitive deficits induced by chronic cerebral hypoperfusion via modulating microglial phenotypic transformation in mice DOI Creative Commons
Weiwei Ji,

Zengyu Zhang,

Ting Jin

et al.

Journal of Neuroimmunology, Journal Year: 2025, Volume and Issue: 400, P. 578544 - 578544

Published: Jan. 31, 2025

Language: Английский

Citations

0
Edaravone dexborneol alleviates pericyte-mediated fibrosis depositing extracellular matrix through TGF-β1/IL-11 in cerebral small vessel disease DOI Creative Commons

Qingrui Duan,

Zhiyang Liu,

Yu-Xuan Xing

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 5, 2025

Chronic cerebral hypoperfusion (CCH) is a critical pathophysiological mechanism underlying small vessel disease (CSVD). Accumulating evidence have demonstrated that resident pericytes and deposit extracellular matrix (ECM) play key role in mediating fibrosis hypoxic changes. Edaravone dexborneol (EDB) known to target multiple pathways involved fibrosis. We constructed the CCH mouse models were subjected either PBS or EDB at different concentrations. Measures of cognitive function, neuronal damage, white matter lesion (WML), fibrous profiles ECM protein investigated assess effect EDB. RNA sequencing OGD was performed identify signaling pathway. observed both medium high concentrations could ameliorate CCH-induced impairment emotional disorders. Neuronal damage cortical layer hippocampus WML corpus callosum improved by EDB, which consistent with tends proteins these regions. suggested TGF-β1/IL-11 plays an important Subsequently, results confirmed cellular model. Our findings reveal pericyte-mediated depositing pathogenesis CSVD. improve symptoms mice decrease expression proteins, may be regulated TGF-β1/ IL-11. treatment, targeting fibrosis, novel therapeutic strategy for

Language: Английский

Citations

0
Edaravone reduces brain injury in hepatic encephalopathy by upregulation of Nrf2/HO-1 and inhibition of NF-κB, iNOS/NO and inflammatory cytokines DOI
Keyvan Amirshahrokhi, Mahsa Imani

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Feb. 12, 2025

Language: Английский

Citations

0
Cerebral Small Vessel Disease: Current and Emerging Therapeutic Strategies DOI Creative Commons

Yuewen Sun,

Xiaoqian Song,

C. J. Jin

et al.

Aging and Disease, Journal Year: 2025, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2025

Cerebral small vessel disease (CSVD) is a common in older people, characterized by damage to intracranial microvessels, leading cognitive decline, increased risk of stroke, and dementia. This review reviews the current therapeutic approaches for CSVD latest research advances, encompassing traditional pharmacological therapies, emerging targeted interventions grounded pathophysiology, exploratory immune-related treatments, advances genetic research. In addition, role lifestyle modifications management discussed. The emphasizes importance holistic, personalized treatment strategy improve outcomes. More clinical trials are needed validate these treatments optimize individualized options patients.

Language: Английский

Citations

0
Ultrasound-guided renal subcapsular transplantation of mesenchymal stem cells for treatment of acute kidney injury in a minipig model: safety and efficacy evaluation DOI Creative Commons

Tuo Xiao,

Yuhao Chen, Bo Jiang

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 28, 2025

Acute kidney injury (AKI) is a major global public health concern with limited treatment options. While preclinical studies have suggested the potential of mesenchymal stem cells (MSCs) to repair and protect injured kidneys in AKI, clinical trials using transarterial MSCs transplantation yielded disappointing results. This study aimed investigate feasibility safety minimally invasive renal subcapsular for treating AKI minipig model, ultimately aiming facilitate translation this approach. A novel model was established by combining cisplatin hydration evaluate effectiveness therapies. Renal catheterization successfully achieved under ultrasound guidance. Subsequently, efficacy assessed, biological role tryptophan metabolite kynurenine (Kyn) elucidated through both vivo vitro experiments. The method pre-hydration at 4% body weight, followed post-cisplatin (3.8 mg/kg) 2% cisplatin-induced survival time exceeding 28 days, closely mimicking characteristics typical patients. Additionally, we discovered that multiple transplantations promoted function recovery more effectively than single via catheter. Furthermore, elevated levels Kyn were observed during which activated aryl hydrocarbon receptor (AhR)-mediated NF-κB/NLRP3/IL-1β signaling pathway tubular epithelial cells, thereby exacerbating inflammatory injury. Ultrasound-guided safe effective therapeutic approach bring about significant advancements future.

Language: Английский

Citations

0
Identification of novel inflammatory response-related biomarkers in patients with ischemic stroke based on WGCNA and machine learning DOI Creative Commons
Chenyi Huang,

Dengxuan Wu,

Guifen Yang

et al.

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: March 22, 2025

Ischemic stroke (IS) is one of the most common causes disability in adults worldwide. This study aimed to identify key genes related inflammatory response provide insights into mechanisms and management IS. Transcriptomic data for IS were downloaded from Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) differential expression used inflammation-related (IRGs) associated with Hub IRGs screened using Lasso, SVM-RFE, random forest algorithms, a nomogram diagnostic model was constructed. The performance assessed receiver operating characteristic (ROC) curves calibration plots. Additionally, immune cell infiltration potential small molecule drugs targeting analyzed. IRG verified by qRT-PCR healthy controls patients. Nine differentially expressed identified IS, including NMUR1, AHR, CD68, OSM, CDKN1A, RGS1, BTG2, ATP2C1, TLR3. Machine learning algorithms selected three hub (AHR, NMUR1). A based on these showed excellent an area under curve (AUC) greater than 0.9 both training validation sets. Immune revealed higher levels neutrophils activated CD4 + T cells, lower CD8 NK naive B cells exhibited significant correlations infiltration. Furthermore, identified, chrysin, piperine, genistein, resveratrol, which have therapeutic effects evaluation demonstrated that blood biomarkers NMUR1) patients could serve as distinguishing indicators between (P < 0.05). confirmed impact progression provided new targets personalized treatment

Language: Английский

Citations

0
Limosilactobacillus reuteri DSM17938 Attenuates Neuroinflammatory Responses After Spinal Cord Injury by Modulating Tryptophan Metabolism DOI Creative Commons

Qiuyu Cen,

Yanru Cui,

Jing Feng

et al.

Probiotics and Antimicrobial Proteins, Journal Year: 2025, Volume and Issue: unknown

Published: April 26, 2025

Spinal cord injury (SCI) disrupts gut flora and exacerbates neuroinflammation. Evidence supports the important role of intestinal microbiota in SCI. This study evaluated neuroprotective effect Limosilactobacillus reuteri (L. reuteri) DSM 17938 on SCI its potential anti-inflammatory mechanism. The was disorganised following SCI, with a significant decrease abundance probiotic bacteria such as L. reuteri. DSM17938 treatment improved spinal pathology enhanced locomotor functional recovery SCI-model rats. Moreover, it modulated tryptophan metabolism by promoting indole-3-carboxaldehyde production. In addition, inhibits polarization M1 microglia reduces production IL-6, IL-1 β, TNF-α to alleviate It also activates aryl hydrocarbon receptor (AhR) signalling via upregulating AhR CYP1A1 expression, tight junction protein synthesis. summary, promotes modulating activate barrier repair attenuate microglial activation neuroinflammation, suggesting strategy for clinical adjuvant treatment.

Language: Английский

Citations

0