Blood–Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(16), С. 12699 - 12699

Опубликована: Авг. 11, 2023

The blood-brain barrier, which is formed by tightly interconnected microvascular endothelial cells, separates the brain from peripheral circulation. Together with other central nervous system-resident cell types, including pericytes and astrocytes, barrier forms neurovascular unit. Upon neuroinflammation, this becomes leaky, allowing molecules cells to enter potentially harm tissue of system. Despite significance animal models in research, they may not always adequately reflect human pathophysiology. Therefore, are needed. This review will provide an overview terms both health disease. It describe all key elements vitro explore how different compositions can be utilized effectively model a variety neuroinflammatory conditions. Furthermore, it existing types that used basic research study respective pathologies thus far.

Язык: Английский

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Neurovascular dysfunction in glaucoma

Progress in Retinal and Eye Research, Год журнала: 2023, Номер 97, С. 101217 - 101217

Опубликована: Сен. 30, 2023

Retinal ganglion cells, the neurons that die in glaucoma, are endowed with a high metabolism requiring optimal provision of oxygen and nutrients to sustain their activity. The timely regulation blood flow is, therefore, essential supply firing active areas glucose they need for energy. Many glaucoma patients suffer from vascular deficits including reduced flow, impaired autoregulation, neurovascular coupling dysfunction, blood-retina/brain-barrier breakdown. These processes tightly regulated by community cells known as unit comprising neurons, endothelial pericytes, Müller astrocytes, microglia. In this review, takes center stage we examine ability its members regulate interactions how function might be altered during glaucomatous stress. Pericytes receive special attention based on recent data demonstrating key role physiological pathological conditions. Of particular interest is discovery characterization tunneling nanotubes, thin actin-based conduits connect distal which play roles complex spatial temporal distribution within retinal capillary network. We discuss cellular molecular mechanisms pathophysiological implications, while highlighting opportunities develop strategies protection regeneration improve functional outcomes glaucoma.

Язык: Английский

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Obesity-induced blood-brain barrier dysfunction: phenotypes and mechanisms

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Апрель 27, 2024

Abstract Obesity, a burgeoning global health issue, is increasingly recognized for its detrimental effects on the central nervous system, particularly concerning integrity of blood-brain barrier (BBB). This manuscript delves into intricate relationship between obesity and BBB dysfunction, elucidating underlying phenotypes molecular mechanisms. We commence with an overview BBB’s critical role in maintaining cerebral homeostasis pathological alterations induced by obesity. By employing comprehensive literature review, we examine structural functional modifications context obesity, including increased permeability, altered transport mechanisms, inflammatory responses. The highlights how obesity-induced systemic inflammation metabolic dysregulation contribute to disruption, thereby predisposing individuals various neurological disorders. further explore potential pathways, such as oxidative stress endothelial cell that mediate these changes. Our discussion culminates summary current findings identification knowledge gaps, paving way future research directions. review underscores significance understanding dysfunction not only implications neurodegenerative diseases but also developing targeted therapeutic strategies mitigate effects.

Язык: Английский

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Growth hormone promotes myelin repair after chronic hypoxia via triggering pericyte-dependent angiogenesis

Neuron, Год журнала: 2024, Номер 112(13), С. 2177 - 2196.e6

Опубликована: Апрель 22, 2024

Язык: Английский

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Pharmacological Advances in Incretin-Based Polyagonism: What We Know and What We Don’t

Physiology, Год журнала: 2024, Номер 39(3), С. 142 - 156

Опубликована: Фев. 14, 2024

The prevalence of obesity continues to rise in both adolescents and adults, parallel is strongly associated with the increased incidence type 2 diabetes, heart failure, certain types cancer, all-cause mortality. In relation obesity, many pharmacological approaches past have tried failed combat rising epidemic, particularly due insufficient efficacy or unacceptable side effects. However, while history antiobesity medication plagued by failures disappointments, we witnessed over last 10 years substantial progress, regard biochemically optimized agonists at receptor for glucagon-like peptide-1 (GLP-1R) unimolecular coagonists receptors GLP-1 glucose-dependent insulinotropic polypeptide (GIP). Although GIP receptor:GLP-1R are being heralded as premier tools treatment uncertainty remains why these drugs testify superiority best-in-class GLP-1R monoagonists. Particularly GIP, there great if how acts on systems metabolism system should be activated inhibited improve metabolic outcome adjunct agonism. this review, summarize recent advances GLP-1- GIP-based pharmacology discuss findings open questions related affects systemic energy glucose metabolism.

Язык: Английский

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The Unexpected Role of the Endothelial Nitric Oxide Synthase at the Neurovascular Unit: Beyond the Regulation of Cerebral Blood Flow

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 9071 - 9071

Опубликована: Авг. 21, 2024

Nitric oxide (NO) is a highly versatile gasotransmitter that has first been shown to regulate cardiovascular function and then exert tight control over much broader range of processes, including neurotransmitter release, neuronal excitability, synaptic plasticity. Endothelial NO synthase (eNOS) usually far from the mind neurophysiologists, who have focused most their attention on (nNOS) as primary source at neurovascular unit (NVU). Nevertheless, available evidence suggests eNOS could also contribute generating burst that, serving volume intercellular messenger, produced in response activity brain parenchyma. Herein, we review role both regulation cerebral blood flow plasticity discuss mechanisms by which cerebrovascular endothelial cells may transduce inputs into signal. We further suggest play critical vascular-to-neuronal communication integrating signals converging onto streaming active neurons.

Язык: Английский

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Early intervention with pericyte Fli-1 post-TBI attenuates hippocampal BBB disruption and subsequent neuroinflammation with neurological deficits

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер unknown, С. 167671 - 167671

Опубликована: Янв. 1, 2025

Язык: Английский

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Control of neurovascular coupling by ATP-sensitive potassium channels

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Янв. 17, 2025

Regional blood flow within the brain is tightly coupled to regional neuronal activity, a process known as neurovascular coupling (NVC). In this study, we demonstrate striking role of SUR2- and Kir6.1-dependent ATP-sensitive potassium (KATP) channels in control NVC sensory cortex conscious mice, response mechanical stimuli. We that either globally increased (pinacidil-activated) or decreased (glibenclamide-inhibited) KATP activity markedly disrupts NVC; pinacidil-activation capable completely abolishing stimulus-evoked cortical hemodynamic responses, while glibenclamide slows reduces response. The similarly slowed reduced SUR2 KO animals, animals expressing gain-of-function (GOF) mutations Kir6.1, which underlie Cantú syndrome, exhibit baseline reduction well sensitivity pinacidil. revealing dramatic effects increasing decreasing SUR2/Kir6.1-dependent on NVC, whether pharmacologically genetically induced, study has important implications both for monogenic channel diseases more common pathologies.

Язык: Английский

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Unveiling the native architecture of adult cardiac tissue using the 3D-NaissI method

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Фев. 5, 2025

Accurately imaging adult cardiac tissue in its native state is essential for regenerative medicine and understanding heart disease. Current fluorescence methods encounter challenges with fixation. Here, we introduce the 3D-NaissI (3D-Native Tissue Imaging) method, which enables rapid, cost-effective of fresh samples their closest state, has been extended to other tissues. We validated efficacy preserving integrity using small biopsies under hypothermic conditions phosphate-buffered saline, offering unparalleled resolution confocal microscopy fluorescent molecules antibodies. Compared conventional histology, preserves architecture protein epitopes, facilitating use a wide range commercial antibodies without unmasking strategies. successfully identified specific expression patterns cardiomyocytes (CMs) from rodents humans, including first time ACE2 localization lateral membrane/T-Tubules SGTL2 sarcoplasmic reticulum. These findings shed light on COVID-19-related complications suggest novel explanations therapeutic benefits iSGLT2 HFpEF patients. Additionally, challenge notion "connexin-43 lateralization" pathology, suggesting it may be an artifact fixation, as clearly revealed connexin-43 at membrane healthy CMs. also discovered previously undocumented periodic ring-like 3D structures formed by pericytes that cover surfaces structures, positive laminin-2, delineate spatial laminin-2 receptors CM surface, underscoring pivotal role function. Lastly, facilitates mapping human autopsies, insights into both pathological non-pathological contexts. Therefore, provides biology holds promise advancing our physiology pathophysiology, surpassing standard histology accuracy.

Язык: Английский

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Emerging role of mesenchymal cells in cardiac and cerebrovascular diseases: Physiology, pathology, and therapeutic implications

Vascular Pharmacology, Год журнала: 2025, Номер unknown, С. 107473 - 107473

Опубликована: Фев. 1, 2025

Язык: Английский

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