The contribution of β-amyloid, Tau and α-synuclein to blood–brain barrier damage in neurodegenerative disorders

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

Опубликована: Фев. 12, 2024

Abstract Central nervous system (CNS) accumulation of fibrillary deposits made Amyloid β (A ), hyperphosphorylated Tau or α -synuclein ( -syn), present either alone in the form mixed pathology, characterizes most common neurodegenerative diseases (NDDs) as well aging brain. Compelling evidence supports that acute neurological disorders, such traumatic brain injury (TBI) and stroke, are also accompanied by increased deposition toxic A , -syn species. While contribution these pathological proteins to neurodegeneration has been experimentally ascertained, cellular molecular mechanisms driving -syn-related damage remain be fully clarified. In last few years, studies have shown may contribute inducing and/or promoting blood–brain barrier (BBB) disruption. These can affect BBB integrity directly affecting key components pericytes endothelial cells (ECs) indirectly, macrophages activation dysfunction. Here, we summarize critically discuss findings showing how NDDs, TBI stroke. We highlight need for a deeper characterization role dysfunction macrophages, ECs improve diagnosis treatment chronic disorders.

Язык: Английский

---

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

---

The immunology of stroke and dementia

Immunity, Год журнала: 2025, Номер 58(1), С. 18 - 39

Опубликована: Янв. 1, 2025

Язык: Английский

---

Transcriptome analysis reveals that the injection of mesenchymal stem cells remodels extracellular matrix and complement components of the brain through PI3K/AKT/FOXO1 signaling pathway in a neuroinflammation mouse model

Genomics, Год журнала: 2025, Номер 117(3), С. 111033 - 111033

Опубликована: Март 22, 2025

Язык: Английский

---

Brain endothelial cells as phagocytes: mechanisms and implications

Fluids and Barriers of the CNS, Год журнала: 2025, Номер 22(1)

Опубликована: Апрель 1, 2025

Abstract Brain microvascular endothelial cells (BECs) lining the brain capillaries form anatomical site of blood-brain barrier (BBB), providing a highly selective to support homeostasis and function. While BBB acts as immune pathogens under normal conditions, BECs can facilitate their entry into CNS via phagocytosis-like mechanism. A similar process is now increasingly reported for diverse set cargos, resulting in categorization “non-professional” phagocytes redefining conventional view that these are functionally non-phagocytic. This review aims summarize research demonstrating capacity phagocytose various including aged red blood (RBC), myelin debris, embolic particles. Mechanistically, BEC phagocytosis be triggered by exposure phosphatidylserine on RBC, expression adhesion molecules such ICAM-1 VCAM-1 BECs, cargo-opsonization, and/or involve cytoskeleton remodeling. Phagocytic activity has significant clinical implications ranging from regulation cerebral patency (particularly contributing resolving capillary stalling), clearance parenchymal invasion pathogens. Further, which represents cell (RBC)-in-cell (BEC) phenomenon, implicated hemorrhagic lesions microhemorrhages. shed light an important function within system will delve underlying mechanisms, discuss implications, identify gaps our understanding this phenomenon.

Язык: Английский

---

CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology

Acta Neuropathologica Communications, Год журнала: 2024, Номер 12(1)

Опубликована: Март 18, 2024

Abstract Intracerebral aneurysms (IAs) are pathological dilatations of cerebral arteries whose rupture leads to subarachnoid hemorrhage, a significant cause disability and death. Inflammation is recognized as critical contributor the formation, growth, IAs; however, its precise actors have not yet been fully elucidated. Here, we report CNS-associated macrophages (CAMs), also known border-associated macrophages, one key players in IA pathogenesis, acting mediators inflammatory processes related ruptures. Using new mouse model middle artery (MCA) show that CAMs accumulate walls. This finding was confirmed human MCA aneurysm obtained after surgical clipping, together with other characteristics found experimental including morphological changes cell infiltration. In addition, vivo longitudinal molecular MRI studies revealed vascular inflammation strongly associated area, i.e., high expression VCAM-1 P-selectin adhesion molecules, which precedes predicts bleeding extent case rupture. Specific CAM depletion by intracerebroventricular injection clodronate liposomes prior induction reduced formation rate. Moreover, absence ameliorated outcome severity ruptures resulting smaller hemorrhages, accompanied neutrophil Our data shed light on unexplored role main orchestrating progression IAs towards rupture-prone state. Graphical abstract

Язык: Английский

---

Infections in the Etiology of Parkinson’s Disease and Synucleinopathies: A Renewed Perspective, Mechanistic Insights, and Therapeutic Implications

Journal of Parkinson s Disease, Год журнала: 2024, Номер unknown, С. 1 - 29

Опубликована: Сен. 25, 2024

Increasing evidence suggests a potential role for infectious pathogens in the etiology of synucleinopathies, group age-related neurodegenerative disorders including Parkinson’s disease (PD), multiple system atrophy and dementia with Lewy bodies. In this review, we discuss link between infections synucleinopathies from historical perspective, present emerging that supports link, address current research challenges focus on neuroinflammation. Infectious can elicit neuroinflammatory response modulate genetic risk PD related synucleinopathies. The mechanisms how might be linked as well overlap immune cellular pathways affected by virulent disease-related factors are discussed. Here, an important α-synuclein against is emerging. Critical methodological knowledge gaps addressed, provide new future perspectives to these gaps. Understanding neuroinflammation influence will essential development early diagnostic tools novel therapies.

Язык: Английский

---

Macrophages and endothelial cells in the neurovascular unit

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

Опубликована: Фев. 12, 2024

Язык: Английский

---

Responses of Endothelial Progenitor Cells to Chronic and Acute Physical Activity in Healthy Individuals

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 6085 - 6085

Опубликована: Май 31, 2024

Endothelial progenitor cells (EPCs) are circulating of various origins that possess the capacity for renewing and regenerating endothelial lining blood vessels. During physical activity, in response to factors such as hypoxia, changes osmotic pressure, mechanical forces, undergo intense physiological stress results damage. Circulating EPCs participate vessel repair vascular healing mainly through paracrine signalling. Furthermore, activity may play an important role mobilising this cell population. In narrative review, we summarise current knowledge on biology EPCs, including their characteristics, assessment, mobilisation both chronic acute healthy individuals.

Язык: Английский

---

Protective role of aconitate decarboxylase 1 in neuroinflammation-induced dysfunctions of the paraventricular thalamus and sleepiness

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Ноя. 10, 2024

Sleepiness is commonly associated with neuroinflammation; however, the underlying neuroregulatory mechanisms remain unclear. Previous research suggests that paraventricular thalamus (PVT) plays a crucial role in regulating sleep-wake dynamics; thus, neurological abnormalities PVT may contribute to neuroinflammation-induced sleepiness. To test this hypothesis, we performed electroencephalography recordings mice treated lipopolysaccharide (LPS) and found exhibited temporary sleepiness lasting for 7 days. Using Fos-TRAP method, fiber photometry recordings, immunofluorescence staining, detected neuron hypoactivation microglia activation from day 1 post-LPS treatment. Combining results of bulk single-cell RNA sequencing, upregulation aconitate decarboxylase (Acod1) investigate Acod1, manipulated Acod1 gene expression via stereotactic injection short hairpin adenovirus. Knockdown exacerbated inflammation, neuronal hypoactivation, Itaconate metabolite synthesized by enzyme encoded Acod1. Finally, confirmed exogenous administration an itaconate derivative, 4-octyl itaconate, could inhibit activation, alleviate dysfunction, relieve Our findings highlight PVT's inflammation-induced suggest as potential therapeutic target neuroinflammation.

Язык: Английский

---