Mitochondrial oxidative stress in brain microvascular endothelial cells: Triggering blood-brain barrier disruption

Wang, Yi; Wu, Jing; Wang, Jiexin; He, Li-Xian; Lai, Han; Zhang, Tian; Wang, Xin; Li, Weihong

doi:10.1016/j.mito.2023.01.007

Cited by 19 publications

(11 citation statements)

References 176 publications

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“…Mitochondrial oxidative stress of brain endothelial cells has been linked to BBB disruption [46]. To assess the barrier function in vitro, we determined the effect of Sigma-1R activation on the electrical resistance of the RBMVEC monolayer using ECIS, a method that allows the monitoring of resistance over longer periods of time, while maintaining cells in stable conditions [47,48].…”

Section: Discussionmentioning

confidence: 99%

Modulation of the Blood–Brain Barrier by Sigma-1R Activation

Brailoiu,

Barr,

Wittorf

et al. 2024

IJMS

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Sigma non-opioid intracellular receptor 1 (Sigma-1R) is an intracellular chaperone protein residing on the endoplasmic reticulum at the mitochondrial-associated membrane (MAM) region. Sigma-1R is abundant in the brain and is involved in several physiological processes as well as in various disease states. The role of Sigma-1R at the blood–brain barrier (BBB) is incompletely characterized. In this study, the effect of Sigma-1R activation was investigated in vitro on rat brain microvascular endothelial cells (RBMVEC), an important component of the blood–brain barrier (BBB), and in vivo on BBB permeability in rats. The Sigma-1R agonist PRE-084 produced a dose-dependent increase in mitochondrial calcium, and mitochondrial and cytosolic reactive oxygen species (ROS) in RBMVEC. PRE-084 decreased the electrical resistance of the RBMVEC monolayer, measured with the electric cell-substrate impedance sensing (ECIS) method, indicating barrier disruption. These effects were reduced by pretreatment with Sigma-1R antagonists, BD 1047 and NE 100. In vivo assessment of BBB permeability in rats indicates that PRE-084 produced a dose-dependent increase in brain extravasation of Evans Blue and sodium fluorescein brain; the effect was reduced by the Sigma-1R antagonists. Immunocytochemistry studies indicate that PRE-084 produced a disruption of tight and adherens junctions and actin cytoskeleton. The brain microcirculation was directly visualized in vivo in the prefrontal cortex of awake rats with a miniature integrated fluorescence microscope (aka, miniscope; Doric Lenses Inc.). Miniscope studies indicate that PRE-084 increased sodium fluorescein extravasation in vivo. Taken together, these results indicate that Sigma-1R activation promoted oxidative stress and increased BBB permeability.

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Section: Discussionmentioning

confidence: 99%

Modulation of the Blood–Brain Barrier by Sigma-1R Activation

Brailoiu,

Barr,

Wittorf

et al. 2024

IJMS

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“…The mitochondrial structure is dynamic and balanced between fission and fusion processes, which determine not only mitochondrial shape but also mitochondrial functions, including performance, ROS production, and quality control [99]. The term 'mitochondrial quality control (MQC) system' has been established for this network, which tightly balances mitochondrial dynamics, i.e., fission and fusion events and mitophagy [100,101]. Mitochondrial fission is mainly regulated by cytoplasmic dynamin-related protein 1 (DRP1) with the assistance of numerous factors, including mitochondrial fission protein 1 (FIS1), mitochondrial fission factor (MFF), and mitochondrial dynamic proteins (MID49 and MID51) located at the outer membrane [102,103].…”

Section: Mitochondrial Structure and Dynamics In Endothelial Cellsmentioning

confidence: 99%

“…Mitochondrial dysfunction is characterized by a loss of efficiency in the ETC, resulting in reduced synthesis of high-energy molecules, such as ATP [137], increased ROS generation, and oxidative stress [15]. Mitochondrial dysfunction is associated with aging as well as many chronic diseases, including CVD, neurodegenerative disorders (NDDs), metabolic diseases, and chronic infections [16][17][18][19][20]100,[138][139][140][141]. The following subsections will describe the mechanisms of dysfunction in ECs and the mitochondrial contribution to CVD, NDDs, and DM.…”

Section: Unveiling Endothelial Mitochondrial Dysfunction In Pathophys...mentioning

confidence: 99%

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Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells

Kulovic-Sissawo,

Tocantins,

Diniz

et al. 2024

Biology

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Endothelial dysfunction is associated with several lifestyle-related diseases, including cardiovascular and neurodegenerative diseases, and it contributes significantly to the global health burden. Recent research indicates a link between cardiovascular risk factors (CVRFs), excessive production of reactive oxygen species (ROS), mitochondrial impairment, and endothelial dysfunction. Circulating endothelial progenitor cells (EPCs) are recruited into the vessel wall to maintain appropriate endothelial function, repair, and angiogenesis. After attachment, EPCs differentiate into mature endothelial cells (ECs). Like ECs, EPCs are also susceptible to CVRFs, including metabolic dysfunction and chronic inflammation. Therefore, mitochondrial dysfunction of EPCs may have long-term effects on the function of the mature ECs into which EPCs differentiate, particularly in the presence of endothelial damage. However, a link between CVRFs and impaired mitochondrial function in EPCs has hardly been investigated. In this review, we aim to consolidate existing knowledge on the development of mitochondrial and endothelial dysfunction in the vascular endothelium, place it in the context of recent studies investigating the consequences of CVRFs on EPCs, and discuss the role of mitochondrial dysfunction. Thus, we aim to gain a comprehensive understanding of mechanisms involved in EPC deterioration in relation to CVRFs and address potential therapeutic interventions targeting mitochondrial health to promote endothelial function.

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“…The network model was coded with the BrainPy library in Python [114,115]. All simulations were performed by using the fourth-order Runge-Kutta method (RK4) with a fixed time step of 0.01 ms. A shorter simulation time step does not change the results.…”

Section: Simulation Toolmentioning

confidence: 99%

Spindle Oscillation Emerges at the Critical State of the Electrically Coupled Network in Thalamic Reticular Nucleus

Li,

Wang,

2024

Preprint

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Spindle oscillation is a waxing-and-waning neural oscillation observed in the brain, initiated at the thalamic reticular nucleus (TRN) and typically occurring at 7 – 15 Hz. Recent experiments revealed that in the adult brain, electrical synapses, rather than chemical synapses, are dominating between TRN neurons, indicating that the traditional view of spindle generation via chemical synapses in the TRN needs to be revised. Here, based on the known experimental data, we develop a computational model of the TRN network, in which heterogeneous neurons are connected by electrical synapses. The model consists of two driving forces competing to shape the network dynamics: electrical synapses tend to synchronize neurons, while heterogeneity tends to desynchronize neurons. We demonstrate that the interplay between two forces leads to a network state where multiple synchronized clusters with slightly different oscillation frequencies coexist. In this state, the superposition of neuronal activities gives rise to spindle oscillation, as observed in local field potentials in experiments. Notably, we discover that when TRN neurons generate spindle oscillation, the network operates at the critical state, known for facilitating efficient information processing in complex systems. Our study sheds light on the underlying mechanism of spindle oscillation and its functional significance in neural information processing.

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Mitochondrial oxidative stress in brain microvascular endothelial cells: Triggering blood-brain barrier disruption

Cited by 19 publications

References 176 publications

Modulation of the Blood–Brain Barrier by Sigma-1R Activation

Modulation of the Blood–Brain Barrier by Sigma-1R Activation

Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells

Spindle Oscillation Emerges at the Critical State of the Electrically Coupled Network in Thalamic Reticular Nucleus

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