Activation of TRPV4 channels promotes the loss of cellular ATP in organotypic slices of the mouse neocortex exposed to chemical ischemia

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 601(14), P. 2975 - 2990

Published: May 17, 2023

The vertebrate brain has an exceptionally high energy need. During ischemia, intracellular ATP concentrations decline rapidly, resulting in the breakdown of ion gradients and cellular damage. Here, we employed nanosensor ATeam1.03

Language: Английский

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Spatiotemporal transcriptomic map of glial cell response in a mouse model of acute brain ischemia

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(46)

Published: Nov. 5, 2024

The role of nonneuronal cells in the resolution cerebral ischemia remains to be fully understood. To decode key molecular and cellular processes that occur after ischemia, we performed spatial single-cell transcriptomic profiling male mouse brain during first week injury. Cortical gene expression was severely disrupted, defined by inflammation cell death lesion core, glial scar formation orchestrated multiple types on periphery. identified as a zone with intense cell–cell communication, prominent ApoE-Trem2 signaling pathway modulating microglial activation. For each three major populations, an inflammatory-responsive state, resembling reactive states observed neurodegenerative contexts, observed. recovered spectrum ischemia-induced oligodendrocyte supports emerging hypothesis oligodendrocytes actively respond modulate neuroinflammatory stimulus. findings are further supported analysis other datasets from different models ischemic Collectively, present landmark dataset accompanied interactive visualization provides comprehensive view spatiotemporal organization postischemic brain.

Language: Английский

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Inhibiting Mitochondrial Damage for Efficient Treatment of Cerebral Ischemia‐Reperfusion Injury Through Sequential Targeting Nanomedicine of Neuronal Mitochondria in Affected Brain Tissue

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(50)

Published: Nov. 6, 2024

Abstract Oxidative stress, predominantly from neuronal mitochondrial damage and the resultant cytokine storm, is central to cerebral ischemia‐reperfusion injury (CIRI). However, delivering drugs mitochondria remains challenging due blood‐brain barrier (BBB), which impedes drug entry into affected brain tissues. This study introduces an innovative tannic acid (TA) melanin‐modified heteropolyacid nanomedicine (MHT), highly specifically eliminates reactive oxygen radicals burst efficiently reduce through a strategically designed sequential targeting strategy tissue mitochondria. TA endows MHT with ability by binding matrix proteins exposed damaged BBB outer membrane of neurons, while melanin significantly enhances antioxidant capacity MHT. Consequently, effectively inhibits apoptosis protecting reversing inflammatory immune environment deactivation cyclic GMP‐AMP synthase–stimulator interferon genes (cGAS‐STING) pathway. demonstrated strong therapeutic effect on CIRI, ultralow dose (2 mg kg −1 ) proving effective in condition. work not only new avenue CIRI therapy but also offers paradigm for treating other diseases.

Language: Английский

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Cortical brain organoid slices (cBOS) for the study of human neural cells in minimal networks

iScience, Journal Year: 2024, Volume and Issue: 27(4), P. 109415 - 109415

Published: March 4, 2024

Brain organoids derived from human pluripotent stem cells are a promising tool for studying neurodevelopment and related disorders. Here, we generated long-term cultures of cortical brain organoid slices (cBOS) grown at the air-liquid interphase regionalized organoids. We show that cBOS host mature neurons astrocytes organized in complex architecture. Whole-cell patch-clamp demonstrated subthreshold synaptic inputs action potential firing neurons. Spontaneous intracellular calcium signals turned into synchronous large-scale oscillations upon combined disinhibition NMDA receptors blocking GABA

Language: Английский

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Extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest: an overview of current practice and evidence

Netherlands Heart Journal, Journal Year: 2024, Volume and Issue: 32(4), P. 148 - 155

Published: Feb. 20, 2024

Abstract Cardiac arrest (CA) is a common and potentially avoidable cause of death, while constituting substantial public health burden. Although survival rates for out-of-hospital cardiac (OHCA) have improved in recent decades, the prognosis refractory OHCA remains poor. The use veno-arterial extracorporeal membrane oxygenation during cardiopulmonary resuscitation (ECPR) increasingly being considered to support rescue measures when conventional (CPR) fails. ECPR enables immediate haemodynamic respiratory stabilisation patients with CA who are CPR thereby reduces low-flow time, promoting favourable neurological outcomes. In case OHCA, multiple studies shown beneficial effects specific patient categories. However, might be more effective if it implemented pre-hospital setting reduce limiting permanent brain damage. ongoing ON-SCENE trial provide definitive answer regarding effectiveness ECPR. aim this narrative review present most literature available on its current developments.

Language: Английский

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Improving Outcomes After Post–Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation

Resuscitation, Journal Year: 2024, Volume and Issue: 201, P. 110196 - 110196

Published: June 27, 2024

Language: Английский

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Biomimetic nanocomplexes orchestrate post-stroke cerebral microenvironment via microglia-targeted siRNA delivery

Nano Today, Journal Year: 2024, Volume and Issue: 58, P. 102444 - 102444

Published: Aug. 15, 2024

Language: Английский

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Value of EEG in outcome prediction of hypoxic-ischemic brain injury in the ICU: A narrative review

Resuscitation, Journal Year: 2023, Volume and Issue: 189, P. 109900 - 109900

Published: July 5, 2023

Abstract

Prognostication of comatose patients after cardiac arrest aims to identify with a large probability favourable or unfavouble outcome, usually within the first week event. Electroencephalography (EEG) is technique that increasingly used for this purpose and has many advantages, such as its non-invasive nature possibility monitor evolution ofbrain function over time. At same time, use EEG in critical care environment faces number challenges. This narrative review describes current role future applications outcome prediction postanoxic encephalopathy.

Language: Английский

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Single-nucleus RNA sequencing revealed the impact of post-mortem interval on the cellular component and gene expression analysis of mouse brains

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Abstract Accurate analysis of cell atlas and gene expression in biological tissues using single-nucleus RNA sequencing (snRNA-seq) is dependent on the quality source material, post-mortem interval (PMI) one major sources variation quality. Although use RNA-degraded transcriptome remains controversial, such samples are sometimes sole means to address specific questions. Current studies impact PMI data limited large-scale RNA-seq, which ignores cellular heterogeneity. Thus, deciphering non-cell- autonomous effects caused by imperative for understanding molecular disruption it elicits. Here, we investigated components snRNA-seq from mouse brain post-mortem. We collected that were allowed decay varying amounts time at 25°C prior snRNA-seq, covering entire range RIN values. The different degradation rate mRNA rRNA within nuclei, presented a more stable state. Multi-channel revealed preferential transient depletion oligodendrocytes OPCs with increasing PMI. In addition, rapid widespread overregulation ribosomal recruitment protein (RP) genes various cells, reached plateau 36h. state neuronal cells was not detected, reported significant upregulation PMI-dependent RP its subpopulations their loss. Moreover, showed greatest differential greater perturbation, speculated aberrant these might be associated death. this study, systematically changes profile tissue induced single-cell resolution, important factors responsible changes. our complemented possible explanation postmortem hypoxia-ischemia, provided reference samples.

Language: Английский

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Neural progenitor cell-derived exosomes in ischemia/reperfusion injury in cardiomyoblasts

BMC Neuroscience, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 5, 2025

Abstract The physiologic relationship between the brain and heart is emerging as a novel therapeutic target for clinical intervention acute myocardial infarction. In adult human brain, vestigial neuronal progenitor stem cells contribute to repair recovery following cerebral ischemic injury, an effect modulated by secreted exosomes. Ischemia conditioned cell derived supernatant experimental stroke has been shown be injurious heart. However, whether unconditioned derived-exosomes can instead protect myocardium represents profound research gap. We investigated effects of neural exosomes post-injury treatment cardiomyoblasts from three culture conditions; adherent cultures, neurosphere cultures bioreactor cultures. Small extracellular vesicles were enriched with serial ultracentrifugation, validated via nanoparticle tracking analysis, transmission electron microscopy Western blot analysis prior utilization H9c2 oxygen glucose deprivation. LDH assay was used assess viability Seahorse XF high-resolution respirometry analyzer investigate cardiomyocyte bioenergetics. found no evidence that are cardiotoxic nor cardioprotective ischemia-reperfusion injury. Based on our findings, utilizing other organs should not have adverse damaged cardiac cells.

Language: Английский

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