Microglial polarization in Alzheimer's disease: Mechanisms, implications, and therapeutic opportunities

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β plaques, neurofibrillary tangles, and chronic neuroinflammation. Microglial cells, resident immune cells in central nervous system, play crucial role pathogenesis AD. Microglia can undergo polarization, shifting between pro-inflammatory (M1) anti-inflammatory (M2) phenotypes response to different stimuli. Dysregulation microglial polarization towards phenotype leads release inflammatory cytokines, oxidative stress, synaptic dysfunction. These processes contribute neuronal damage cognitive decline However, several challenges remain this field. The complex molecular mechanisms governing AD need be further elucidated. In review, we discuss underlying its implications progression.

Language: Английский

---

Blood-brain barrier repair: potential and challenges of stem cells and exosomes in stroke treatment

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: April 7, 2025

Stroke is characterized with high morbidity, mortality and disability all over the world, one of its core pathologies blood-brain barrier (BBB) dysfunction. BBB plays a crucial physiological role in protecting brain tissues maintaining homeostasis central nervous system (CNS). dysfunction serves as key factor development cerebral edema, inflammation, further neurological damage stroke patients. Currently, stem cells their derived exosomes have shown remarkable potential repairing damaged improving function after stroke. Stem repair integrity through anti-inflammatory, antioxidant, angiogenesis regulation intercellular signaling mechanisms, while cell-derived exosomes, natural nanocarriers, enhance therapeutic effect by carrying active substances such proteins, RNAs miRNAs. This review will present latest research advances treatment, well challenges cell source, transplantation timing, dosage, route administration clinical application, aiming to discuss mechanisms for proposes future directions. are expected provide new strategies early diagnosis precise treatment stroke, promote breakthroughs field

Language: Английский

---

Astrocyte-derived IL11 modulates astrocytes-microglia crosstalk via NF-κB signaling pathway in sepsis-associated encephalopathy

Research, Journal Year: 2025, Volume and Issue: 8

Published: Jan. 1, 2025

Sepsis-associated encephalopathy (SAE) is a severe and frequent septic complication, characterized by neuronal damage as key pathological features. The astrocyte–microglia crosstalk in the central nervous system (CNS) plays important roles various neurological diseases. However, how astrocytes interact with microglia to regulate injury SAE poorly defined. In this study, we aim investigate molecular basis of underlying pathogenesis also explore new therapeutic strategies targeting devastating disease. We established human astrocyte/microglia coculture on microfluidic device, which allows real-time high-resolution recording glial responses inflammatory stimuli. Based system, can test lipopolysaccharide (LPS) treatment, identify cues that mediate condition. addition, mouse model was utilized determine state cells evaluate effect drugs vivo. Here, found activated exhibited close spatial interaction model. Upon LPS exposure for astrocytes, detected more migrated astrocyte culture compartment accompanied M1 polarization increased cell motility microglia. Cytokine array analysis revealed less interleukin 11 (IL11) secreted following further promoted reprogramming pro-inflammatory phenotype via nuclear factor-κB (NF-κB) signaling pathway. Intriguingly, IL11 addition markedly rescued LPS-induced injuries brain This study defines an unknown mediated IL11, contributed neuropathogenesis SAE, suggested potential value

Language: Английский

---

Regulatory T Cells for Stroke Recovery: A Promising Immune Therapeutic Strategy

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 1, 2025

ABSTRACT Background Stroke remains a leading cause of mortality and disability among adults. Given the restricted therapeutic window for intravascular interventions neuroprotection during acute phase, there has been growing focus on tissue repair functional recovery in subacute chronic phases after stroke. The pro‐inflammatory microglial polarization occurs stroke may represent targets recovery. CD4 + regulatory T cells (Tregs), subtype with immunosuppressive effects, have shown to be important Tregs infiltrate into brain primarily following Infiltrating play critical role mitigating responses, modulating immune microenvironment, promoting restoration damaged Methods A systematic literature search was conducted PubMed, Scopus, Web Science then conduct comprehensive analysis searched literature. Results This review provides summary recent preclinical research advances stroke, particular their reparative functions phases. It discusses changes peripheral infiltrating post‐stroke, underlying mechanisms, strategies involving Tregs. Additionally, this explores potential challenges associated clinical application ischemic Conclusion Treg cell‐related therapy represents promising immune‐therapeutic strategy However, are several issues that must resolved before its advancement application.

Language: Английский

---

Lycorine Pre-Treatment Alleviates Microglia Inflammation After Cerebral Ischemia by Inhibiting NF-κB Phosphorylation

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(3), P. 290 - 290

Published: March 9, 2025

Background: Middle-aged and elderly individuals may experience detrimental health effects due to ischemic stroke (IS). The inflammatory response triggered during IS exacerbates neuronal damage, becoming a barrier effective treatment leading poor patient prognosis. Nevertheless, the specific role of microglia in by remains mostly unclear. primary target this investigation is study neuroinflammatory impact lycorine (LYC) process. Our objective evaluate whether LYC deploys its anti-inflammatory effect with modulation NF-κB signaling pathway, thereby reducing symptoms. Methods: In research, BV-2 cells were pre-treated for 24 h before LPS was added induce inflammation. Results: It has been discovered that suppresses cell polarization reduces levels cytokines (IL-1β, IL-6, TNF-α), showing potential vitro. Furthermore, IκBα p65 play crucial roles regulating within pathway. Mechanistic exploration indicates can activate expression LPS-induced cells. inhibits binding subunit, sequestering it cytoplasm preventing translocation nucleus, inhibiting Additionally, key transcription factor pro-inflammatory genes, downregulation leads decreased transcriptional activity these genes. combined increased results significantly reduced activity, alleviating response. Meanwhile, vivo studies indicate pre-treatment infarct size caused middle cerebral artery occlusion (MCAO) rats. assessment infarction volume, neurological scores, brain edema rate inflammation MCAO rats positive therapeutic effects. Conclusions: summary, our research significant attenuating through inhibition, which contributes benefits (IS) improve disease serve as an adjunctive clinical IS, be confirmed trials future.

Language: Английский

---

Remote Organ Damage Induced by Stroke: Molecular Mechanisms and Comprehensive Interventions

Antioxidants and Redox Signaling, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Significance: Damage after stroke is not only limited to the brain but also often occurs in remote organs, including heart, lung, liver, kidney, digestive tract, and spleen, which are frequently affected by complex pathophysiological changes. The organs human body closely connected, signals transmitted through various molecular substances could regulate changes of organs. Recent Advances: latest studies have shown that inflammatory response plays an important role organ damage stroke, can aggravate activating oxidative stress, sympathetic axis, hypothalamic disturbing immunological homeostasis. Remote cause brain, aggravating damage. Critical Issues: Therefore, in-depth exploration mechanisms adopting corresponding comprehensive intervention strategies become necessary reduce promote protection. Future Directions: strategy involves multifaceted treatment methods such as inflammation regulation, antioxidants, neural stem cell differentiation. It provides a promising alternative for recovery patients inspiration future research treatment. interconnected at level. Only levels we save protect greatest extent. Antioxid. Redox Signal. 00, 000-000.

Language: Английский

---

Ershen Zhenwu Decoction Suppresses Myocardial Fibrosis of Chronic Heart Failure with Heart–Kidney Yang Deficiency by Down-Regulating the Ras Homolog Gene Family Member A/Rho-Associated Coiled-Coil Kinases Signaling Pathway

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 340, P. 119146 - 119146

Published: Nov. 22, 2024

Language: Английский

---

Physical Exercise Improves the Neuronal Function in Ischemic Stroke Via Microglial CB2R/P2Y12 Signaling

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: July 27, 2024

Language: Английский

---

miR-133b Regulates Blood-Brain Barrier Permeability after Cerebral Ischemia-Reperfusion Mediated by RohA Signaling Pathway

Hans Journal of Biomedicine, Journal Year: 2024, Volume and Issue: 14(03), P. 426 - 434

Published: Jan. 1, 2024

Language: Английский

---