The niche matters: origin, function and fate of CNS-associated macrophages during health and disease

Acta Neuropathologica, Год журнала: 2024, Номер 147(1)

Опубликована: Фев. 12, 2024

Abstract There are several cellular and acellular structural barriers associated with the brain interfaces, which include dura, leptomeninges, perivascular space choroid plexus epithelium. Each structure is enriched by distinct myeloid populations, mainly originate from erythromyeloid precursors (EMP) in embryonic yolk sac seed CNS during embryogenesis. However, depending on precise microanatomical environment, resident cells differ their marker profile, turnover extent to they can be replenished blood-derived cells. While some EMP-derived parenchyma become microglia, others engraft meninges CNS-associated macrophages (CAMs), also referred as border-associated (BAMs), e.g., leptomeningeal (MnMΦ). Recent data revealed that MnMΦ migrate into spaces postnatally where differentiate (PvMΦ). Under homeostatic conditions pathogen-free mice, there virtually no contribution of bone marrow-derived PvMΦ, but rather dura. In neuropathological blood–brain barrier compromised, however, an influx occur, potentially contributing pool Simultaneously, CAMs may proliferate undergo transcriptional proteomic changes, thereby, disease outcome. Thus, both infiltrating together act within microenvironmental niche , populations play crucial roles overall course. Here, we summarize current understanding sources fates health disease, role microenvironment influencing maintenance function.

Язык: Английский

---

Blood-brain barrier disruption: a culprit of cognitive decline?

Fluids and Barriers of the CNS, Год журнала: 2024, Номер 21(1)

Опубликована: Авг. 7, 2024

Cognitive decline covers a broad spectrum of disorders, not only resulting from brain diseases but also systemic diseases, which seriously influence the quality life and expectancy patients. As highly selective anatomical functional interface between circulation, blood-brain barrier (BBB) plays pivotal role in maintaining homeostasis normal function. The pathogenesis underlying cognitive may vary, nevertheless, accumulating evidences support BBB disruption as most prevalent contributing factor. This mainly be attributed to inflammation, metabolic dysfunction, cell senescence, oxidative/nitrosative stress excitotoxicity. However, direct evidence showing that causes is scarce, interestingly, manipulation opening alone exert beneficial or detrimental neurological effects. A overview present literature shows close relationship decline, risk factors disruption, well cellular molecular mechanisms disruption. Additionally, we discussed possible leading by potential therapeutic strategies prevent enhance repair. review aims foster more investigations on early diagnosis, effective therapeutics, rapid restoration against would yield better outcomes patients with dysregulated function, although their causative has yet been completely established.

Язык: Английский

---

Endothelial cells and macrophages as allies in the healthy and diseased brain

Acta Neuropathologica, Год журнала: 2024, Номер 147(1)

Опубликована: Фев. 12, 2024

Abstract Diseases of the central nervous system (CNS) are often associated with vascular disturbances or inflammation and frequently both. Consequently, endothelial cells macrophages key cellular players that mediate pathology in many CNS diseases. Macrophages brain consist CNS-associated (CAMs) [also referred to as border-associated (BAMs)] microglia, both which close neighbours even form direct contacts microvessels. Recent progress has revealed different macrophage populations a subset derived from same erythromyeloid progenitor cells. share several common features their life cycle—from invasion into early during embryonic development proliferation CNS, demise. In adults, microglia CAMs have been implicated regulating patency diameter vessels, blood flow, tightness blood–brain barrier, removal calcification, life-time Conversely, may affect polarization activation state myeloid populations. The molecular mechanisms governing pas de deux beginning be deciphered will reviewed here.

Язык: Английский

---

Role of Oxidative Stress in Blood–Brain Barrier Disruption and Neurodegenerative Diseases

Antioxidants, Год журнала: 2024, Номер 13(12), С. 1462 - 1462

Опубликована: Ноя. 28, 2024

Upregulation of reactive oxygen species (ROS) levels is a principal feature observed in the brains neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s (AD). In these diseases, oxidative stress can disrupt blood–brain barrier (BBB). This disruption allows neurotoxic plasma components, blood cells, pathogens to enter brain, leading increased ROS production, mitochondrial dysfunction, inflammation. Collectively, factors result protein modification, lipid peroxidation, DNA damage, and, ultimately, neural cell damage. this review article, we present mechanisms by which damage leads BBB breakdown brain diseases. Additionally, summarize potential therapeutic approaches aimed at reducing that contributes

Язык: Английский

---

Brain MRI Detection of an Abnormal Peak Width of Skeletonized Mean Diffusivity in REM Sleep Behavior Disorder

Journal of Neuroimaging, Год журнала: 2025, Номер 35(1)

Опубликована: Янв. 1, 2025

ABSTRACT Background and Purpose Peak width of skeletonized mean diffusivity (PSMD) is a novel marker white matter damage, which may be related to small vessel disease. This study aimed investigate the presence damage in patients with isolated rapid eye movement sleep behavior disorder (RBD) using PSMD. Methods We enrolled newly diagnosed RBD confirmed by polysomnography age‐ sex‐matched healthy controls. Diffusion tensor imaging (DTI) was conducted 3‐Tesla MRI scanner. measured PSMD based on DTI several steps, including preprocessing, skeletonization, application custom mask, histogram analysis, Functional Magnetic Resonance Imaging Brain Software Library program. compared incidence between controls performed correlation analysis clinical factors RBD. Results Thirty 41 were enrolled. The significantly higher than that (3.078 vs. 2.746 × 10 −4 mm 2 /s, p = 0.001). In addition, positively correlated age ( r 0.477, 0.007). However, not associated other or polysomnographic factors. Conclusion Patients had controls, indicating evidence finding highlights potential as for detecting diseases, disorders.

Язык: Английский

---

Physical activity and neuroplasticity in neurodegenerative disorders: a comprehensive review of exercise interventions, cognitive training, and AI applications

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Фев. 28, 2025

This review aimed to elucidate the mechanisms through which (i) physical activity (PA) enhances neuroplasticity and cognitive function in neurodegenerative disorders, (ii) identify specific PA interventions for improving rehabilitation programs. We conducted a literature search PubMed, Medline, Scopus, Web of Science, PsycINFO, covering publications from January 1990 August 2024. The strategy employed key terms related neuroplasticity, exercise, function, personalized activity. Inclusion criteria included original research on relationship between while exclusion eliminated studies focusing solely pharmacological interventions. identified multiple pathways may enhance including releasing neurotrophic factors, modulation neuroinflammation, reduction oxidative stress, enhancement synaptic connectivity neurogenesis. Aerobic exercise was found increase hippocampal volume by 1–2% improve executive scores 5–10% older adults. Resistance training enhanced control memory performance 12–18% elderly individuals. Mind–body exercises, such as yoga tai-chi, improved gray matter density memory-related brain regions 3–5% emotional regulation 15–20%. Dual-task attention processing speed 8–14% individuals with disorders. also discuss potential role AI-based AI preventing rehabilitating illnesses, highlighting innovative approaches patient outcomes. significantly disorders various mechanisms. resistance training, mind–body practices, dual-task exercises each offer unique benefits. Implementing these activities clinical settings can Future should focus creating tailored conditions, incorporating programs optimize rehabilitation.

Язык: Английский

---

Postbiotics as Molecules Targeting Cellular Events of Aging Brain—The Role in Pathogenesis, Prophylaxis and Treatment of Neurodegenerative Diseases

Nutrients, Год журнала: 2024, Номер 16(14), С. 2244 - 2244

Опубликована: Июль 12, 2024

Aging is the most prominent risk factor for neurodegeneration occurrence. The common neurodegenerative diseases (NDs), Alzheimer’s (AD) and Parkinson’s (PD) diseases, are characterized by incidence of proteinopathy, abnormal activation glial cells, oxidative stress, neuroinflammation, impaired autophagy cellular senescence excessive patient’s age. Moreover, mitochondrial disfunction, epigenetic alterations neurogenesis inhibition, together with increased blood–brain barrier permeability gut dysbiosis, have been linked to ND pathogenesis. Since NDs still lack curative treatment, recent research has sought therapeutic options in restoring microbiota supplementing probiotic bacteria-derived metabolites beneficial action host—so called postbiotics. current review focuses on literature explaining mechanisms involved pathogenesis addressing impact that postbiotics as a whole mixture particular metabolites, such short-chain fatty acids (SCFAs), lactate, polyamines, polyphenols, tryptophan exopolysaccharides bacterial extracellular vesicles, ageing-associated processes underlying also discusses issue implementing into prophylaxis therapy, depicting them compounds senescence-triggered dysfunctions worth translating from bench pharmaceutical market response “silver consumers” demands.

Язык: Английский

---

Oligomeric Tau-induced oxidative damage and functional alterations in cerebral endothelial cells: Role of RhoA/ROCK signaling pathway

Free Radical Biology and Medicine, Год журнала: 2024, Номер 221, С. 261 - 272

Опубликована: Май 28, 2024

Despite of yet unknown mechanism, microvascular deposition oligomeric Tau (oTau) has been implicated in alteration the Blood-Brain Barrier (BBB) function Alzheimer's disease (AD) brains. In this study, we employed an vitro BBB model using primary mouse cerebral endothelial cells (CECs) to investigate mechanism underlying effects oTau on function. We found that exposing CECs induced oxidative stress through NADPH oxidase, increased damage proteins, decreased proteasome activity, and expressions tight junction (TJ) proteins including occludin, zonula occludens-1 (ZO-1) claudin-5. These were suppressed by pretreatment with Fasudil, a RhoA/ROCK signaling inhibitor. Consistent biochemical alterations, basolateral side disrupted integrity BBB, as indicated increase FITC-dextran transport across model, decrease trans electrical resistance (TEER). also transmigration peripheral blood mononuclear (PBMCs) model. functional alterations Fasudil. Taken together, our findings suggest targeting pathway can be potential therapeutic strategy maintain AD.

Язык: Английский

---

Pharmacological Activities and Molecular Mechanisms of Sinapic Acid in Neurological Disorders

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(16), С. 2966 - 2981

Опубликована: Июль 31, 2024

Sinapic acid (SA) is a phenylpropanoid derivative found in various natural sources that exhibits remarkable versatile properties, including antioxidant, anti-inflammatory, and metal-chelating capabilities, establishing itself as promising candidate for the prevention treatment of conditions affecting central nervous system, such Alzheimer's disease (AD), Parkinson's (PD), ischemic stroke, other neurological disorders. These effects also include neuroprotection epilepsy models, evidenced by reduction seizure-like behavior, cell death specific hippocampal regions, lowered neuroinflammatory markers. In AD, SA enhances memory, reverses cognitive deficits, attenuates astrocyte activation. has positive on cognition improving memory lowering oxidative stress. This shown lower levels stress markers, higher antioxidant enzyme activity, better retention. Additionally, stroke PD provides microglial protection exerts anti-inflammatory effects. review emphasizes SA's multifaceted neuroprotective properties its potential role brain Despite need further research to fully understand mechanisms action clinical applicability, stands out valuable bioactive compound ongoing quest combat neurodegenerative diseases enhance quality life affected individuals.

Язык: Английский

---

Role of the transcription factor NRF2 in maintaining the integrity of the Blood-Brain Barrier

Fluids and Barriers of the CNS, Год журнала: 2024, Номер 21(1)

Опубликована: Ноя. 21, 2024

The Blood-Brain Barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules cells between blood central nervous system. It undergoes structural functional throughout oxidative stress inflammation, which may compromise its integrity contribute to pathogenesis neurodegenerative diseases. Maintaining BBB utmost importance in preventing wide range neurological disorders. NRF2 main transcription factor cellular redox balance inflammation-related gene expression. has also demonstrated potential role regulating tight junction contributing inhibition ECM remodeling, by reducing expression several metalloprotease family members involved maintaining function. Overall, we review current insights on addressing protection against effects dysfunction, discuss involvement maintenance different neuropathological diseases, as well as, some activators have been used vitro vivo animal models for barrier dysfunction. Thus, emerging evidence suggests upregulation target genes could suppress stress, neuroinflammation, restore integrity, increase protection.

Язык: Английский

---