β2 integrin regulates neutrophil trans endothelial migration following traumatic brain injury

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 8, 2025

Neutrophils are the first responders among peripheral immune cells to infiltrate central nervous system following a traumatic brain injury (TBI), triggering neuroinflammation that can exacerbate secondary tissue damage. The precise molecular controls dictate inflammatory behavior of neutrophils post-TBI, however, remain largely elusive. Our comprehensive analysis landscape surrounding trauma in TBI mice has revealed significant alteration abundance β2 integrin (ITGB2), predominantly expressed by and closely associated with responses. Using fluid percussion (FPI) mouse model, we investigated therapeutic efficacy Rovelizumab, an agent blocks ITGB2. treatment demonstrated improvements neurologic function mice, attenuating blood–brain barrier permeability, mitigating oxidative stress mediator release, enhancing cerebral perfusion. Moreover, ITGB2 blockade effectively limited adherence, migration, infiltration neutrophils, impeded formation neutrophil extracellular traps (NETs) upon their activation. Finally, it was mediates these effects mainly through its interaction intercellular adhesion molecule-1 (ICAM 1) endotheliocyte. These findings collectively illuminate as crucial switch governs adverse post-TBI could be targeted improve clinical outcome patients.

Language: Английский

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Cannabidiol Protects Against Neurotoxic Reactive Astrocytes‐Induced Neuronal Death in Mouse Model of Epilepsy

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(3)

Published: March 1, 2025

ABSTRACT Reactive astrocytes play a critical role in the initiation and progression of epilepsy, but their molecular subtypes functional characterization are not fully understood. In this study, we report existence neurotoxic reactive astrocytes, recently identified subtype, that contribute to neuronal death epileptic brain. kainic acid (KA)‐induced mouse model show induced by microglia‐secreted cytokines, including IL‐1α, TNFα, C1q, detectable as early 7 days post‐KA stimulation. These cells exhibit distinct signature marked elevated expression complement 3 adenosine 2A receptor. Transcriptomics metabolomics analyses human brain tissues from temporal lobe epilepsy (TLE) patients an reveal induce damage through lipid‐related mechanisms. Moreover, our results demonstrate anti‐seizure medication cannabidiol (CBD) receptor antagonist can both suppress formation mitigate gliosis, reduce loss epilepsy. Electrophysiological behavioral studies indicate attenuates seizure symptoms enhances memory capabilities mice. Our findings suggest formed at stage KA‐induced TLE releasing toxic lipids. Importantly, emerges promising therapeutic drug for targeted intervention against adult image

Language: Английский

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Refining the interactions between microglia and astrocytes in Alzheimer’s disease pathology

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Astrocyte heterogeneity in ischemic stroke: Molecular mechanisms and therapeutic targets

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106885 - 106885

Published: March 1, 2025

Language: Английский

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