Loss of direct vascular contact to astrocytes in the hippocampus as an initial event in Alzheimer’s disease. Evidence from patients, in vivo and in vitro experimental models. DOI Creative Commons

Carlos Pomilio,

Jessica Presa, Camila Oses

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Сен. 5, 2023

Abstract Alzheimer's disease (AD) is characterized by the accumulation of aggregated amyloid peptides in brain parenchyma and also around vasculature. The hippocampus -a complex structure with a crucial role learning memory- considered target pathology. However, there scarce information regarding vascular changes during AD neurodegenerative process this vulnerable structure, that unique terms vasculature features. Our aim was to evaluate hippocampal alterations patients PDAPP-J20 mice -model AD- define impact Aβ40 Aβ42 on endothelial activation. We found loss physical astrocyte-endothelium interaction subjects as compared non-AD donors together decreased density. Astrocyte-endothelial interactions levels tight junction protein occludin were early altered mice, before morphological or blood-brain barrier disruption evident. At later stages, showed density extravasation fluorescent tracers, indicating BBB dysfunction. In vitro studies exposure human microvascular cells (HBMEC) soluble sufficient promote NFκB translocation nucleus, leading reduction levels. These prevented treatment HBMEC an inhibitor membrane receptor for advanced glycation endproducts (RAGE). Additional results suggest acts indirectly endothelium inducing astrocytic factors. Furthermore, our from mouse samples provide evidence involvement disease.

Язык: Английский

Noteworthy perspectives on microglia in neuropsychiatric disorders DOI Creative Commons
Hongrui Zhu,

Ao Guan,

Jiayuan Liu

и другие.

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Окт. 4, 2023

Abstract Microglia are so versatile that they not only provide immune surveillance for central nervous system, but participate in neural circuitry development, brain blood vessels formation, blood–brain barrier architecture, and intriguingly, the regulation of emotions behaviors. have a profound impact on neuronal survival, wiring synaptic plasticity. As professional phagocytic cells brain, remove dead cell debris neurotoxic agents via an elaborate mechanism. The functional profile microglia varies considerately depending age, gender, disease context other internal or external environmental factors. Numerous studies demonstrated pivotal involvement neuropsychiatric disorders, including negative affection, social deficit, compulsive behavior, fear memory, pain symptoms associated with major depression disorder, anxiety autism spectrum disorder schizophrenia. In this review, we summarized latest discoveries regarding microglial ontogeny, subtypes state spectrum, biological functions mechanistic underpinnings emotional behavioral disorders. Furthermore, highlight potential microglia-targeted therapies propose outstanding questions to be addressed future research human microglia.

Язык: Английский

Процитировано

42
The glymphatic system: a new perspective on brain diseases DOI Creative Commons

Zhao Ding,

Xiaodi Fan, Yehao Zhang

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Июнь 15, 2023

The glymphatic system is a brain-wide perivascular pathway driven by aquaporin-4 on the endfeet of astrocytes, which can deliver nutrients and active substances to brain parenchyma through periarterial cerebrospinal fluid (CSF) influx remove metabolic wastes perivenous clearance routes. This paper summarizes composition, overall flow, solute transport, related diseases, affecting factors, preclinical research methods system. In doing so, we aim provide direction reference for more relevant researchers in future.

Язык: Английский

Процитировано

26
Simvastatin alleviates glymphatic system damage via the VEGF-C/VEGFR3/PI3K-Akt pathway after experimental intracerebral hemorrhage DOI Creative Commons
Junbo Liao,

Yingxing Duan,

Yaxue Liu

и другие.

Brain Research Bulletin, Год журнала: 2024, Номер 216, С. 111045 - 111045

Опубликована: Авг. 5, 2024

Current clinical practice primarily relies on surgical intervention to remove hematomas in patients with intracerebral hemorrhage (ICH), given the lack of effective drug therapies. Previous research indicates that simvastatin (SIM) may enhance hematoma absorption and resolution acute phase ICH, though precise mechanisms remain unclear. Recent findings have highlighted glymphatic system (GS) as a crucial component intracranial cerebrospinal fluid circulation, playing significant role clearance post-ICH. This study investigates link between SIM efficacy GS. Our experimental results show alleviates GS damage ICH-induced rats, resulting improved outcomes such reduced brain edema, neuronal apoptosis, degeneration. Further analysis reveals SIM's effects are mediated through VEGF-C/VEGFR3/PI3K-Akt pathway. advances our understanding mechanism promoting underscores potential targeting for ICH treatment.

Язык: Английский

Процитировано

18
Piezo1-dependent regulation of pericyte proliferation by blood flow during brain vascular development DOI Creative Commons

Huaxing Zi,

Xiaolan Peng, Jianbin Cao

и другие.

Cell Reports, Год журнала: 2024, Номер 43(1), С. 113652 - 113652

Опубликована: Янв. 1, 2024

Blood flow is known to regulate cerebrovascular development through acting on vascular endothelial cells (ECs). As an indispensable component of the neurovascular unit, brain pericytes physically couple with ECs and play vital roles in blood-brain barrier integrity maintenance coupling. However, it remains unclear whether blood affects pericyte development. Using vivo time-lapse imaging larval zebrafish, we monitored developmental dynamics found that they proliferate expand their population increase coverage vessels. In combination pharmacological genetic approaches, demonstrated enhances proliferation Piezo1 expressed ECs. Moreover, identified EC-intrinsic Notch signaling downstream promote activation pericytes. Thus, our findings reveal a role proliferation, extending functional spectrum hemodynamics

Язык: Английский

Процитировано

14
Echinatin protects from ischemic brain injury by attenuating NLRP3-related neuroinflammation DOI

Liang Sun,

Duo Chen, Chenchen Zhao

и другие.

Neurochemistry International, Год журнала: 2024, Номер 175, С. 105676 - 105676

Опубликована: Фев. 7, 2024

Язык: Английский

Процитировано

9
Anti‐seizure medication response and the glymphatic system in patients with focal epilepsy DOI Creative Commons
Sung Tae Kim, Sung Eun Kim, Dong Ah Lee

и другие.

European Journal of Neurology, Год журнала: 2023, Номер 31(1)

Опубликована: Окт. 12, 2023

We aimed to evaluate (i) glymphatic system function in patients with focal epilepsy comparison healthy controls, and (ii) the association between anti-seizure medication (ASM) response by using diffusion tensor image analysis along perivascular space (DTI-ALPS).

Язык: Английский

Процитировано

13
Neuroprotective effects of Jie-du-huo-xue decoction on microglia pyroptosis after cerebral ischemia and reperfusion——From the perspective of glial-vascular unit DOI Creative Commons
Chang Zhou, Jinxia Li, Caixing Zheng

и другие.

Journal of Ethnopharmacology, Год журнала: 2023, Номер 318, С. 116990 - 116990

Опубликована: Авг. 1, 2023

Ischemic stroke poses a serious risk to public health and quality of life. Jie-Du-Huo-Xue decoction (JDHXD) is classical well-known Chinese formula for treatment, but the pharmacological mechanism still unclear.This study aims investigate underlying microglial pyroptosis polarization, as well potential efficacy JDHXD against cerebral ischemia-reperfusion injury (CIRI).Models CIRI were established by middle artery occlusion/reperfusion (MCAO/R) method in rats. In first stage, 36 SD rats randomly divided into sham group, I/R JDHXD-L group (5.36 g/kg/day), JDHXD-M (10.71 JDHXD-H (21.42 positive drug edaravone group. The effectiveness on was confirmed neurological function testing infarct measuring. best dose (JDXHD-M) subsequently chosen perform tests that followed. second Detection nerve damage using Nissl staining, proteins pyroptosis, Iba-1, NeuN expressions detected western blotting, M1/M2 phenotypic polarization immunofluorescence.In after CIRI, significantly reduced impairment infarction. addition, facilitated M1-to-M2 transition microglia order minimize neuroinflammation improve anti-inflammatory repair. JDXHD inhibited blocking cleavage caspase-1 P10 gasdermin D, hence reducing neuronal enhancing survival following reperfusion. Interestingly, also demonstrated protective effect glial-vascular unit (GVU).Our investigation exerted GVU-protective decreasing neuroinflammation-associated suppressing M1 activation, promoting M2 activation.

Язык: Английский

Процитировано

11
Loss of Direct Vascular Contact to Astrocytes in the Hippocampus as an Initial Event in Alzheimer’s Disease. Evidence from Patients, In Vivo and In Vitro Experimental Models DOI

Carlos Pomilio,

José Presa, Camila Oses

и другие.

Molecular Neurobiology, Год журнала: 2024, Номер 61(8), С. 5142 - 5160

Опубликована: Янв. 3, 2024

Язык: Английский

Процитировано

3
Carotid artery transplantation of brain endothelial cells enhances neuroprotection and neurorepair in ischaemic stroke rats DOI
Yiting Du,

Zhiguang Pan,

B. Chen

и другие.

Acta Pharmacologica Sinica, Год журнала: 2024, Номер 45(12), С. 2487 - 2496

Опубликована: Июль 11, 2024

Язык: Английский

Процитировано

3
Enlarged perivascular spaces correlate with blood-brain barrier leakage and cognitive impairment in Alzheimer's disease DOI Creative Commons
Wen Chen, Jinghuan Gan, Shuai Liu

и другие.

Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown

Опубликована: Фев. 9, 2025

Background The clinical significance of enlarged perivascular spaces (EPVS) in Alzheimer’ s disease (AD) was ambiguous. Objective To investigate whether EPVS contribute to blood-brain barrier (BBB) leakage and cognition AD. Methods study included a total 64 participants (26 healthy controls 38 patients with AD). evaluation BBB permeability performed specific anatomical locations: the centrum semiovale (CSO), basal ganglia, hippocampus. ratings were according Potter's instructions. evaluated using dynamic contrast-enhanced-MRI. relationship between global (Mini-Mental State Examination Montreal Cognitive Assessment), cognitive subdomains, examined both groups. Finally, CSO AD investigated. Results High-grade found associated (OR: 3.40, 95% CI: 1.11–11.90, p = 0.04). In group, significant correlation observed high-grade lower MMSE score (r −0.36, 0.03) verbal fluency −0.44, 0.01). positively correlated 0.58, < 0.001). negatively −0.52, 0.001) attention −0.40, Conclusions is related leakage, which contributes impairment patients, especially frequency. can function as convenient marker for intervention therapy.

Язык: Английский

Процитировано

0