Development of blood-brain barrier under the modulation of HIF activity in astroglial and neuronal cells in vitro

Ruzaeva, V A; Моргун, А. В.; Хилажева, Е. Д.; Кувачева, Н. В.; Пожиленкова, Е. А.; Boitsova, Elizaveta B.; Мартынова, Г. П.; Таранушенко, Т. Е.; Салмина, А. Б.

doi:10.18097/pbmc20166206664

Cited by 12 publications

(4 citation statements)

References 21 publications

(29 reference statements)

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“…Brain endothelial cells, pericytes, neuron and astrocytes all express HIF-1α. Endothelial cells exhibited greater response to ischemic injury in the upregulation of HIF-1α expression compared to astrocytes and pericytes [80–83]. Other studies supported that brain endothelial cell HIF-1α can directly regulate the expression of occludin and ZO-1, albeit with controversial outcome [84–86].…”

Section: Discussionmentioning

confidence: 99%

Endothelial progenitor cells transplantation attenuated blood-brain barrier damage after ischemia in diabetic mice via HIF-1α

Geng

Wang

et al. 2017

Stem Cell Res Ther

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BackgroundBlood-brain barrier impairment is a major indicator of endothelial dysfunction in diabetes. Studies showed that endothelial progenitor cell (EPC) transplantation promoted angiogenesis and improved function recovery after hind limb ischemia in diabetic mice. The effect of EPC transplantation on blood-brain barrier integrity after cerebral ischemia in diabetic animals is unknown. The aim of this study is to explore the effect of EPC transplantation on the integrity of the blood-brain barrier after cerebral ischemia in diabetic mice.MethodsEPCs were isolated by density gradient centrifugation and characterized by flow cytometry and immunostaining. Diabetes was induced in adult male C57BL/6 mice by a single injection of streptozotocin at 4 weeks before surgery. Diabetic mice underwent 90-minute transient middle cerebral artery occlusion surgery and received 1 × 106 EPCs transplantation immediately after reperfusion. Brain infarct volume, blood-brain barrier permeability, tight junction protein expression, and hypoxia inducible factor-1α (HIF-1α) mRNA level were examined after treatment.ResultsWe demonstrated that neurological deficits were attenuated and brain infarct volume was reduced in EPC-transplanted diabetic mice after transient cerebral ischemia compared to the controls (p < 0.05). Blood-brain barrier leakage and tight junction protein degradation were reduced in EPC-transplanted mice (p <0.05). EPCs upregulated HIF-1α expression while HIF-1α inhibitor PX-478 abolished the beneficial effect of EPCs.ConclusionsWe conclude that EPCs protected blood-brain barrier integrity after focal ischemia in diabetic mice through upregulation of HIF-1α signaling.

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Section: Discussionmentioning

confidence: 99%

Endothelial progenitor cells transplantation attenuated blood-brain barrier damage after ischemia in diabetic mice via HIF-1α

Geng

Wang

et al. 2017

Stem Cell Res Ther

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“…Many events in intercellular interactions at the BBB level are determined by the activity of the transcription factor HIF-1, which mediates the cellular response to hypoxia [142]. It is known that HIF-1-induced reactions in energy metabolism are reflected in changes in glycolysis processes, lactate accumulation, and alterations in the nature of neuron-astroglial metabolic coupling [143].…”

Section: Maintenance Of Selective Permeability Of the Blood-brain Bar...mentioning

confidence: 99%

Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia

Tregub,

Kulikov,

Ibrahimli

et al. 2024

IJMS

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The review introduces the stages of formation and experimental confirmation of the hypothesis regarding the mutual potentiation of neuroprotective effects of hypoxia and hypercapnia during their combined influence (hypercapnic hypoxia). The main focus is on the mechanisms and signaling pathways involved in the formation of ischemic tolerance in the brain during intermittent hypercapnic hypoxia. Importantly, the combined effect of hypoxia and hypercapnia exerts a more pronounced neuroprotective effect compared to their separate application. Some signaling systems are associated with the predominance of the hypoxic stimulus (HIF-1α, A1 receptors), while others (NF-κB, antioxidant activity, inhibition of apoptosis, maintenance of selective blood–brain barrier permeability) are mainly modulated by hypercapnia. Most of the molecular and cellular mechanisms involved in the formation of brain tolerance to ischemia are due to the contribution of both excess carbon dioxide and oxygen deficiency (ATP-dependent potassium channels, chaperones, endoplasmic reticulum stress, mitochondrial metabolism reprogramming). Overall, experimental studies indicate the dominance of hypercapnia in the neuroprotective effect of its combined action with hypoxia. Recent clinical studies have demonstrated the effectiveness of hypercapnic–hypoxic training in the treatment of childhood cerebral palsy and diabetic polyneuropathy in children. Combining hypercapnic hypoxia with pharmacological modulators of neuro/cardio/cytoprotection signaling pathways is likely to be promising for translating experimental research into clinical medicine.

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“…Using BMECs but not ECs of other origin as a part of the models is more physiological to reproduce the main mechanisms of BBB development and functioning. As we have shown before, specific metabolic properties of BMECs makes them an interesting object for managing the barrier permeability in BBB models, or even in tissue models based on the cerebral endothelial monolayer (i.e., neurogenic niche in vitro model) [ 123 , 139 , 140 , 141 , 142 , 143 , 144 ].…”

Section: Application Of In Vitro Nvu/bbb Models For Studying Mitochondria-related Changes In Cell Metabolism: Current Trends and Challengmentioning

confidence: 99%

Blood–Brain Barrier and Neurovascular Unit In Vitro Models for Studying Mitochondria-Driven Molecular Mechanisms of Neurodegeneration

Салмина

Kharitonova

Gorina

et al. 2021

IJMS

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Pathophysiology of chronic neurodegeneration is mainly based on complex mechanisms related to aberrant signal transduction, excitation/inhibition imbalance, excitotoxicity, synaptic dysfunction, oxidative stress, proteotoxicity and protein misfolding, local insulin resistance and metabolic dysfunction, excessive cell death, development of glia-supported neuroinflammation, and failure of neurogenesis. These mechanisms tightly associate with dramatic alterations in the structure and activity of the neurovascular unit (NVU) and the blood–brain barrier (BBB). NVU is an ensemble of brain cells (brain microvessel endothelial cells (BMECs), astrocytes, pericytes, neurons, and microglia) serving for the adjustment of cell-to-cell interactions, metabolic coupling, local microcirculation, and neuronal excitability to the actual needs of the brain. The part of the NVU known as a BBB controls selective access of endogenous and exogenous molecules to the brain tissue and efflux of metabolites to the blood, thereby providing maintenance of brain chemical homeostasis critical for efficient signal transduction and brain plasticity. In Alzheimer’s disease, mitochondria are the target organelles for amyloid-induced neurodegeneration and alterations in NVU metabolic coupling or BBB breakdown. In this review we discuss understandings on mitochondria-driven NVU and BBB dysfunction, and how it might be studied in current and prospective NVU/BBB in vitro models for finding new approaches for the efficient pharmacotherapy of Alzheimer’s disease.

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Development of blood-brain barrier under the modulation of HIF activity in astroglial and neuronal cells in vitro

Cited by 12 publications

References 21 publications

Endothelial progenitor cells transplantation attenuated blood-brain barrier damage after ischemia in diabetic mice via HIF-1α

Endothelial progenitor cells transplantation attenuated blood-brain barrier damage after ischemia in diabetic mice via HIF-1α

Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia

Blood–Brain Barrier and Neurovascular Unit In Vitro Models for Studying Mitochondria-Driven Molecular Mechanisms of Neurodegeneration

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