Cell death in experimental intracerebral hemorrhage: The ?black hole? model of hemorrhagic damage

Introduction: Intracerebral hemorrhage (ICH) is a type of stroke caused by the loss of vascular integrity leading to bleeding within the brain tissue. Hematoma-derived factors cause secondary injury mechanisms such as cell death days to weeks after the event and in regions distant from the primary insult. Increasing evidence suggests that hemoglobin released by the hematoma is one of the major contributors to neuronal injury in ICH. To date, it is unclear whether brain endothelial cells (EC) are similarly vulnerable to hemolysis products and undergo regulated cell death. Hypothesis: We hypothesized that brain EC undergo multiple, different modes of cell death after ICH and that the underlying mechanisms are different compared to neurons. Methods: We systematically investigated cell death mechanisms in brain EC after exposure to the hemolysis product hemin. We used chemical inhibitors of apoptosis, autophagy, ferroptosis, necroptosis, and parthanatos and assessed biochemical markers of these cell death modes. Results: Brain EC viability was concentration-dependently decreased, starting at higher hemin concentrations than neurons. Treatment of EC with ferroptosis inhibitors protective against hemin toxicity in neurons and against ICH in vivo showed that only N-acetylcysteine and deferoxamine protected brain EC, while ferrostatin-1 and U0126 did not abrogate EC death. The autophagy inhibitor bafilomycin A1 also reduced EC death and hemin increased the expression of the autophagy marker LC3. While inhibitors against apoptosis and parthanatos were not effective, the necroptosis inhibitor GSK872 demonstrated a partial protective effect. Conclusions: Our data suggest that ICH induces different mechanisms of death in EC (ferroptosis and autophagy) compared to neurons (ferroptosis and necroptosis) and may thus warrant a combinatorial therapeutic approach. Further investigations in human and ovine ICH brain tissue are ongoing.

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AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage

BioMed Research International ◽

10.1155/2018/3706047 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Xiao Lin ◽

Haotuo Ye ◽

Felix Siaw-Debrah ◽

Sishi Pan ◽

Zibin He ◽

...

Keyword(s):

Cell Death ◽

Intracerebral Hemorrhage ◽

Cell Damage ◽

Neuronal Cell ◽

Neurological Function ◽

Inflammatory Factors ◽

Neuroprotective Effects ◽

Caspase 1 ◽

Cell Death Pathways ◽

Cell Death Pathway

Intracerebral hemorrhage (ICH) refers to bleeding in the brain and is associated with the release of large amount of inflammasomes, and the activation of different cell death pathways. These cell death pathways lead to removal of inactivated and damaged cells and also result in neuronal cell damage. Pyroptosis is a newly discovered cell death pathway that has gained attention in recent years. This pathway mainly depends on activation of caspase-1-mediated cascades to cause cell death. We tested a well-known selective inhibitor of caspase-1, AC-YVAD-CMK, which has previously been found to have neuroprotective effects in ICH mice model, to ascertain its effects on the activation of inflammasomes mediated pyroptosis. Our results showed that AC-YVAD-CMK could reduce caspase-1 activation and inhibit IL-1β production and maturation, but has no effect on NLRP3 expression, an upstream inflammatory complex. AC-YVAD-CMK administration also resulted in reduction in M1-type microglia polarization around the hematoma, while increasing the number of M2-type cells. Furthermore, AC-YVAD-CMK treated mice showed some recovery of neurological function after hemorrhage especially at the hyperacute and subacute stage resulting in some degree of limb movement. In conclusion, we are of the view that AC-YVAD-CMK could inhibit pyroptosis, decrease the secretion or activation of inflammatory factors, and affect the polarization of microglia resulting in improvement of neurological function after ICH.

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Defect extremal surface for reflected entropy

Journal of High Energy Physics ◽

10.1007/jhep01(2022)018 ◽

2022 ◽

Vol 2022 (1) ◽

Author(s):

Tianyi Li ◽

Ma-Ke Yuan ◽

Yang Zhou

Keyword(s):

Black Hole ◽

Mixed State ◽

Entanglement Entropy ◽

Quantum Defect ◽

Entropy Measure ◽

Extremal Surface ◽

Decomposition Procedure ◽

Hole Model ◽

Quantum Defect Theory

Abstract Defect extremal surface is defined by extremizing the Ryu-Takayanagi formula corrected by the quantum defect theory. This is interesting when the AdS bulk contains a defect brane (or string). We introduce a defect extremal surface formula for reflected entropy, which is a mixed state generalization of entanglement entropy measure. Based on a decomposition procedure of an AdS bulk with a brane, we demonstrate the equivalence between defect extremal surface formula and island formula for reflected entropy in AdS3/BCFT2. We also compute the evolution of reflected entropy in evaporating black hole model and find that defect extremal surface formula agrees with island formula.

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Mimicking Black Holes in General Relativity

10.26686/wgtn.14361101.v1 ◽

2021 ◽

Author(s):

Thomas Berry

Keyword(s):

Black Holes ◽

General Relativity ◽

Black Hole ◽

Thin Shell ◽

Classical General Relativity ◽

Regular Black Hole ◽

Regular Black Holes ◽

Traversable Wormholes ◽

Hole Model ◽

Linearised Stability

The central theme of this thesis is the study and analysis of black hole mimickers. The concept of a black hole mimicker is introduced, and various mimicker spacetime models are examined within the framework of classical general relativity. The mimickers examined fall into the classes of regular black holes and traversable wormholes under spherical symmetry. The regular black holes examined can be further categorised as static spacetimes, however the traversable wormhole is allowed to have a dynamic (non-static) throat. Astrophysical observables are calculated for a recently proposed regular black hole model containing an exponential suppression of the Misner-Sharp quasi-local mass. This same regular black hole model is then used to construct a wormhole via the "cut-and-paste" technique. The resulting wormhole is then analysed within the Darmois-Israel thin-shell formalism, and a linearised stability analysis of the (dynamic) wormhole throat is undertaken. Yet another regular black hole model spacetime is proposed, extending a previous work which attempted to construct a regular black hole through a quantum "deformation" of the Schwarzschild spacetime. The resulting spacetime is again analysed within the framework of classical general relativity. In addition to the study of black hole mimickers, I start with a brief overview of the theory of special relativity where a new and novel result is presented for the combination of relativistic velocities in general directions using quaternions. This is succeed by an introduction to concepts in differential geometry needed for the successive introduction to the theory of general relativity. A thorough discussion of the concept of spacetime singularities is then provided, before analysing the specific black hole mimickers discussed above.

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Self-Regular Black Holes Quantized by means of an Analogue to Hydrogen Atoms

Advances in High Energy Physics ◽

10.1155/2016/5982482 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Chang Liu ◽

Yan-Gang Miao ◽

Yu-Mei Wu ◽

Yu-Hao Zhang

Keyword(s):

Black Holes ◽

Black Hole ◽

Mass Density ◽

Hydrogen Atoms ◽

Quantum Black Hole ◽

Extreme Black Hole ◽

Angular Momenta ◽

Probability Densities ◽

Hoop Conjecture ◽

Hole Model

We suggest a quantum black hole model that is based on an analogue to hydrogen atoms. A self-regular Schwarzschild-AdS black hole is investigated, where the mass density of the extreme black hole is given by the probability density of the ground state of hydrogen atoms and the mass densities of nonextreme black holes are given by the probability densities of excited states with no angular momenta. Such an analogue is inclined to adopt quantization of black hole horizons. In this way, the total mass of black holes is quantized. Furthermore, the quantum hoop conjecture and the Correspondence Principle are discussed.

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Reflective black holes

Modern Physics Letters A ◽

10.1142/s021773232150200x ◽

2021 ◽

pp. 2150200

Author(s):

Revaz Beradze ◽

Merab Gogberashvili ◽

Lasha Pantskhava

Keyword(s):

Black Holes ◽

Black Hole ◽

Gravitational Waves ◽

Gamma Ray ◽

Gamma Ray Bursts ◽

Radio Bursts ◽

Hole Model

In this paper, a brief analysis of repeated and overlapped gamma-ray bursts, fast radio bursts and gravitational waves is done. These signals may not be emitted by isolated cataclysmic events and we suggest interpreting some of them within the impenetrable black hole model, as the radiation reflected and amplified by the black hole horizons.

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The relationship between black hole mass and galaxy properties: examining the black hole feedback model in IllustrisTNG

Monthly Notices of the Royal Astronomical Society ◽

10.1093/mnras/staa374 ◽

2020 ◽

Vol 493 (2) ◽

pp. 1888-1906 ◽

Cited By ~ 23

Author(s):

Bryan A Terrazas ◽

Eric F Bell ◽

Annalisa Pillepich ◽

Dylan Nelson ◽

Rachel S Somerville ◽

...

Keyword(s):

Black Hole ◽

Star Formation ◽

Galaxy Formation ◽

Formation Rate ◽

Black Hole Mass ◽

Star Forming ◽

Stellar Radius ◽

Accretion Rates ◽

Hole Model ◽

Galaxy Population

ABSTRACT Supermassive black hole feedback is thought to be responsible for the lack of star formation, or quiescence, in a significant fraction of galaxies. We explore how observable correlations between the specific star formation rate (sSFR), stellar mass (Mstar), and black hole mass (MBH) are sensitive to the physics of black hole feedback in a galaxy formation model. We use the IllustrisTNG simulation suite, specifically the TNG100 simulation and 10 model variations that alter the parameters of the black hole model. Focusing on central galaxies at z = 0 with Mstar > 1010 M⊙, we find that the sSFR of galaxies in IllustrisTNG decreases once the energy from black hole kinetic winds at low accretion rates becomes larger than the gravitational binding energy of gas within the galaxy stellar radius. This occurs at a particular MBH threshold above which galaxies are found to sharply transition from being mostly star forming to mostly quiescent. As a result of this behaviour, the fraction of quiescent galaxies as a function of Mstar is sensitive to both the normalization of the MBH–Mstar relation and the MBH threshold for quiescence in IllustrisTNG. Finally, we compare these model results to observations of 91 central galaxies with dynamical MBH measurements with the caveat that this sample is not representative of the whole galaxy population. While IllustrisTNG reproduces the observed trend that quiescent galaxies host more massive black holes, the observations exhibit a broader scatter in MBH at a given Mstar and show a smoother decline in sSFR with MBH.

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