Ginsenoside Rh4 Alleviates Amyloid β Plaque and Tau Hyperphosphorylation by Regulating Neuroinflammation and the Glycogen Synthase Kinase 3β Signaling Pathway DOI
Renying Zhuo, Haixia Yang, Chenhui Zhu

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(37), P. 13783 - 13794

Published: Sept. 7, 2023

Alzheimer's disease (AD) is a primary neurodegenerative disease. It can be caused by aging and brain trauma severely affects the abilities of cognition memory patients. Therefore, it seriously threatens mental physical health humans worldwide. As traditional Chinese medicine, ginsenosides have been proven to variety pharmacological activities. Ginsenoside Rh4 (Rh4) one rare with higher activity than ordinary ginsenosides, but its effect on alleviating AD molecular mechanism not studied. Here, we investigated anti-AD effects potential mechanisms using an mouse model induced combination AlCl3·6H2O d-galactose. The results showed that could significantly improve ability cognizance reduce neuronal damage in mice. Concurrently, attenuates amyloid β accumulation, increases density dendritic spines, logically inhibits synaptic structural as result excessive apoptosis autophagy. only inhibit inflammatory response overactivation microglia astrocytes, levels pro-inflammatory factors, increase level antioxidant enzymes serum, enzyme SOD1 hippocampus also hyperphosphorylation tau protein mice regulating Wnt2b/GSK-3β/SMAD4 signaling pathway. Together, this study provides theoretical basis for treatment reveals drug AD.

Language: Английский

VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model DOI Creative Commons
Lígia Simões Braga Boisserand, Luiz Henrique Geraldo, Jean Bouchart

et al.

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(4)

Published: March 5, 2024

Meningeal lymphatic vessels (MLVs) promote tissue clearance and immune surveillance in the central nervous system (CNS). Vascular endothelial growth factor-C (VEGF-C) regulates MLV development maintenance has therapeutic potential for treating neurological disorders. Herein, we investigated effects of VEGF-C overexpression on brain fluid drainage ischemic stroke outcomes mice. Intracerebrospinal administration an adeno-associated virus expressing mouse full-length (AAV-mVEGF-C) increased CSF to deep cervical lymph nodes (dCLNs) by enhancing upregulated neuroprotective signaling pathways identified single nuclei RNA sequencing cells. In a model stroke, AAV-mVEGF-C pretreatment reduced injury ameliorated motor performances subacute stage, associated with mitigated microglia-mediated inflammation BDNF Neuroprotective were lost upon cauterization dCLN afferent lymphatics not mimicked acute post-stroke injection. We conclude that prophylaxis promotes multiple vascular, immune, neural responses culminate protection against damage stroke.

Language: Английский

Citations

20
Bone marrow mesenchymal stem cell-derived exosomal lncRNA KLF3-AS1 stabilizes Sirt1 protein to improve cerebral ischemia/reperfusion injury via miR-206/USP22 axis DOI Creative Commons
Xiaowei Xie, Yu Cao,

Liangping Dai

et al.

Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(1)

Published: Jan. 10, 2023

Cerebral ischemia/reperfusion (I/R) is a pathological process that occurs in ischemic stroke. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been verified to relieve cerebral I/R-induced inflammatory injury. Hence, we intended clarify the function of BMSC-Exos-delivered lncRNA KLF3-AS1 (BMSC-Exos KLF3-AS1) neuroprotection and investigated its potential mechanism. To mimic I/R injury vivo vitro, middle artery occlusion (MCAO) mice model oxygen-glucose deprivation (OGD) BV-2 cell were established. BMSC-Exos administered MCAO or OGD-exposed cells. The modified neurological severity score (mNSS), shuttle box test, cresyl violet staining performed measure neuroprotective functions, while was evaluated with MTT, TUNEL reactive oxygen species (ROS) assays. Targeted genes proteins detected using western blot, qRT-PCR, immunohistochemistry. molecular interactions assessed RNA immunoprecipitation, co-immunoprecipitation luciferase reduced infarction improved mice. Similarly, it also promoted viability, suppressed apoptosis, ROS production cells exposed OGD. upregulated decreased Sirt1 induced by I/R. Mechanistically, inhibited ubiquitination protein through inducing USP22. Additionally, sponged miR-206 upregulate USP22 expression. Overexpression silencing abolished KLF3-AS1-mediated protective effects. deubiquitinating ameliorate via KLF3-AS1/miR-206/USP22 network.

Language: Английский

Citations

35
Cerebral organoids transplantation repairs infarcted cortex and restores impaired function after stroke DOI Creative Commons

Shi-Ying Cao,

Di Yang,

Zhenquan Huang

et al.

npj Regenerative Medicine, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 30, 2023

Stroke usually causes prolonged or lifelong disability, owing to the permanent loss of infarcted tissue. Although a variety stem cell transplantation has been explored improve neuronal defect behavior by enhancing neuroplasticity, it remains unknown whether tissue can be reconstructed. We here cultured human cerebral organoids derived from pluripotent cells (hPSCs) and transplanted them into junction infarct core peri-infarct zone NOD-SCID mice subjected stroke. Months later, we found that grafted survived well in core, differentiated target neurons, repaired tissue, sent axons distant brain targets, integrated host neural circuit thereby eliminated sensorimotor behaviors stroke mice, whereas dissociated single failed repair Our study offers new strategy for reconstructing via reversing stroke-induced disability.

Language: Английский

Citations

32
The central role of peripheral inflammation in ischemic stroke DOI
Molly Monsour, Cesar V. Borlongan

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2023, Volume and Issue: 43(5), P. 622 - 641

Published: Jan. 5, 2023

Stroke pathology and its treatments conventionally focus on the brain. Probing inflammation, a critical secondary cell death mechanism in stroke, has been largely relegated to To this end, peripheral inflammation emerged as an equally potent contributor onset progression of stroke death. Here, we review novel concepts organs displaying robust inflammatory response stroke. These inflammation-plagued include spleen, cervical lymph nodes, thymus, bone marrow, gastrointestinal system, adrenal glands, likely converging their effects through B T-cells. Recognizing significant impact systemic also discuss innovative therapeutics directed at sequestration inflammation. This paper challenges paradigm brain-centered disease treatment offers approach our understanding.

Language: Английский

Citations

26
Photobiomodulation Combined With Human Umbilical Cord Mesenchymal Stem Cells Modulates the Polarization of Microglia DOI

Chunyan Ma,

Hongyu Zhu,

Yuanhao Cai

et al.

Journal of Biophotonics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

ABSTRACT Neuroinflammation plays a key role in the development of neurodegenerative diseases, with microglia regulating this process through pro‐inflammatory M1 and anti‐inflammatory M2 phenotypes. Studies have shown that human umbilical cord mesenchymal stem cells (hUCMSCs) modulate neuroinflammation by secreting cytokines. Photobiomodulation (PBM), non‐invasive therapy, has demonstrated significant potential alleviating neuroinflammation. This study examines combined effects PBM hUCMSCs an vitro microglial inflammation model LPS‐induced mouse model. The results show PBM‐pretreated promoted polarization improved cognitive function mice downregulating Notch signaling pathway, suggesting promising new approach for treating diseases.

Language: Английский

Citations

1
Sex differences in the inflammatory response to stroke DOI
Muhammad Bilal Tariq, Juneyoung Lee, Louise D. McCullough

et al.

Seminars in Immunopathology, Journal Year: 2022, Volume and Issue: 45(3), P. 295 - 313

Published: Nov. 10, 2022

Language: Английский

Citations

34
The Multifaceted Role of Cofilin in Neurodegeneration and Stroke: Insights into Pathogenesis and Targeting as a Therapy DOI Creative Commons
Faheem Shehjar, Daniyah A. Almarghalani, Reetika Mahajan

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 188 - 188

Published: Jan. 18, 2024

This comprehensive review explores the complex role of cofilin, an actin-binding protein, across various neurodegenerative diseases (Alzheimer’s, Parkinson’s, schizophrenia, amyotrophic lateral sclerosis (ALS), Huntington’s) and stroke. Cofilin is essential protein in cytoskeletal dynamics, any dysregulation could lead to potentially serious complications. Cofilin’s involvement underscored by its impact on pathological hallmarks like Aβ plaques α-synuclein aggregates, triggering synaptic dysfunction, dendritic spine loss, impaired neuronal plasticity, leading cognitive decline. In Parkinson’s disease, cofilin collaborates with α-synuclein, exacerbating neurotoxicity impairing mitochondrial axonal function. ALS frontotemporal dementia showcase cofilin’s association genetic factors C9ORF72, affecting actin dynamics contributing neurotoxicity. Huntington’s disease brings into focus microglial migration influencing plasticity through AMPA receptor regulation. Alzheimer’s, schizophrenia exhibit 14-3-3 proteins as a shared mechanism. case stroke, takes center stage, mediating cell death. Notably, there potential overlap pathologies diseases. this context, referencing dysfunction provide valuable insights common associated aforementioned conditions. Moreover, promising therapeutic interventions, including inhibitors gene therapy, demonstrating efficacy preclinical models. Challenges inhibitor development, brain delivery, tissue/cell specificity, long-term safety are acknowledged, emphasizing need for precision drug therapy. The call action involves collaborative research, biomarker identification, advancing translational efforts. emerges pivotal player, offering target. However, unraveling complexities requires concerted multidisciplinary efforts nuanced effective interventions intricate landscape presenting hopeful avenue improved patient care.

Language: Английский

Citations

6
Potential of CBD Acting on Cannabinoid Receptors CB1 and CB2 in Ischemic Stroke DOI Open Access
Iu Raïch, Jaume Lillo, Rafael Rivas‐Santisteban

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6708 - 6708

Published: June 18, 2024

Stroke is one of the leading causes death. It not only affects adult people but also many children. estimated that, every year, 15 million suffer a stroke worldwide. Among them, 5 die, while are left permanently disabled. In this sense, research to find new treatments should be accompanied with therapies combat neuronal death and avoid developing cognitive impairment dementia. Phytocannabinoids among compounds that have been used by mankind for longest period history. Their beneficial effects such as pain regulation or neuroprotection widely known make them possible therapeutic agents high potential. These bind cannabinoid receptors CB

Language: Английский

Citations

6
Mitochondria in Cell-Based Therapy for Stroke DOI Creative Commons
Molly Monsour, Jonah Gordon, Gavin Lockard

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(1), P. 178 - 178

Published: Jan. 12, 2023

Despite a relatively developed understanding of the pathophysiology underlying primary and secondary mechanisms cell death after ischemic injury, there are few established treatments to improve stroke prognoses. A major contributor is mitochondrial dysfunction. Recent advancements in cell-based therapies suggest that stem cells may be revolutionary for treating stroke, reestablishment integrity underlie these therapeutic benefits. In fact, functioning mitochondria imperative reducing oxidative damage neuroinflammation following reperfusion injury. this review, we will discuss role establishing anti-oxidative effects stroke.

Language: Английский

Citations

13
Neuroinflammation in the Evolution of Motor Function in Stroke and Trauma Patients: Treatment and Potential Biomarkers DOI Creative Commons
Ane Larrea, Ane Elexpe, Eguzkiñe Díez-Martín

et al.

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(11), P. 8552 - 8585

Published: Oct. 25, 2023

Neuroinflammation has a significant impact on different pathologies, such as stroke or spinal cord injury, intervening in their pathophysiology: expansion, progression, and resolution. involves oxidative stress, damage, cell death, playing an important role neuroplasticity motor dysfunction by affecting the neuronal connection responsible for control. The diagnosis of this pathology is performed using neuroimaging techniques molecular diagnostics based identifying measuring signaling molecules specific markers. In parallel, new therapeutic targets are being investigated via use bionanomaterials electrostimulation to modulate neuroinflammatory response. These novel diagnostic strategies have potential facilitate development anticipatory patterns deliver most beneficial treatment improve patients’ quality life directly skills. However, challenges remain be solved. Hence, goal study was review implication neuroinflammation evolution function trauma patients, with particular focus methods biomarkers aid clinicians diagnosis, treatment, therapy. A analysis strengths, weaknesses, threats, opportunities conducted, highlighting key faced coming years.

Language: Английский

Citations

12