Targeting pyroptosis with nanoparticles to alleviate neuroinflammatory for preventing secondary damage following traumatic brain injury

Science Advances, Journal Year: 2024, Volume and Issue: 10(2)

Published: Jan. 10, 2024

Posttraumatic neuroinflammation is a key driver of secondary injury after traumatic brain (TBI). Pyroptosis, proinflammatory form programmed cell death, considerably activates strong and amplifies the inflammatory response by releasing contents. Therefore, treatments targeting pyroptosis may have beneficial effects on treatment damage TBI. Here, cysteine-alanine-glutamine-lysine peptide-modified β-lactoglobulin (β-LG) nanoparticle was constructed to deliver disulfiram (DSF), C-β-LG/DSF, inhibit decrease neuroinflammation, thereby preventing TBI-induced injury. In post-TBI mice model, C-β-LG/DSF selectively targets injured brain, increases DSF accumulation, extends time systemic circulation DSF. can alleviate edema response, injury, promote learning, improve memory recovery in trauma. this study likely provided potential approach for reducing spread

Language: Английский

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Combination therapies and other therapeutic approaches targeting the NLRP3 inflammasome and neuroinflammatory pathways: a promising approach for traumatic brain injury

Immunopharmacology and Immunotoxicology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 17

Published: Jan. 6, 2025

Objectives: Traumatic brain injury (TBI) precipitates a neuroinflammatory cascade, with the NLRP3 inflammasome emerging as critical mediator. This review scrutinizes complex activation pathways of by underscoring intricate interplay between calcium signaling, mitochondrial disturbances, redox imbalances, lysosomal integrity, and autophagy. It is hypothesized that combination therapy approach—integrating NF-κB pathway inhibitors antagonists—holds potential to synergistically dampen inflammatory storm associated TBI.

Language: Английский

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Hydroxysafflor yellow a confers neuroprotection against acute traumatic brain injury by modulating neuronal autophagy to inhibit NLRP3 inflammasomes

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 308, P. 116268 - 116268

Published: Feb. 25, 2023

Language: Английский

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Proof-of-Principle Study of Inflammasome Signaling Proteins as Diagnostic Biomarkers of the Inflammatory Response in Parkinson’s Disease

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(6), P. 883 - 883

Published: June 15, 2023

Parkinson's disease (PD) is a neurodegenerative disorder marked by the death of dopaminergic neurons in midbrain, accumulation α-synuclein aggregates, and motor deficits. A major contributor to neuronal loss neuroinflammation. The inflammasome multiprotein complex that perpetuates neuroinflammation disorders including PD. Increases proteins are associated with worsened pathology. Thus, inhibition inflammatory mediators has potential aid PD treatment. Here, we investigated signaling as biomarkers response Plasma from subjects healthy age-matched controls were evaluated for levels protein apoptosis-associated speck-like containing caspase recruitment domain (ASC), caspase-1, interleukin (IL)-18. This was carried out using Simple Plex technology identify changes blood subjects. area under curve (AUC) obtained through calculation receiver operating characteristics (ROC) obtain information on biomarker reliability traits. Additionally, completed stepwise regression selected lowest Akaike criterion (AIC) assess how caspase-1 ASC contribute IL-18 people demonstrated elevated ASC, when compared controls; each these found be promising inflammation Furthermore, determined significantly predict serve reliable provide significant contributions

Language: Английский

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Beneficial Effects of Human Schwann Cell-Derived Exosomes in Mitigating Secondary Damage After Penetrating Ballistic-Like Brain Injury

Journal of Neurotrauma, Journal Year: 2024, Volume and Issue: 41(21-22), P. 2395 - 2412

Published: March 6, 2024

There is a growing body of evidence that the delivery cell-derived exosomes normally involved in intracellular communication can reduce secondary injury mechanisms after brain and spinal cord improve outcomes. Exosomes are nanometer-sized vesicles released by Schwann cells may have neuroprotective effects reducing posttraumatic inflammatory processes as well promoting tissue healing functional recovery. The purpose this study was to evaluate beneficial human Schwann-cell (hSC-Exos) severe model penetrating ballistic-like (PBBI) rats investigate on multiple Human cell processing protocols followed Current Good Manufacturing Practices (cGMP) with exosome extraction purification steps approved FDA for an expanded access single ALS patient IND. Anesthetized male Sprague-Dawley (280-350g) underwent PBBI surgery or sham procedures starting 30 min received either dose hSC-Exos PBS through jugular vein. At 48hrs PBBI, flow cytometry analysis cortical revealed administration reduced number activated microglia levels caspase-1, marker inflammasome activation. Neuropathological at 21 days showed treatment significantly overall contusion volume decreased frequency Iba-1 positive amoeboid immunocytochemical analysis. This systemic TBI reduces histopathological damage. represents clinically relevant cell-based therapy limit detrimental neurotrauma other progressive neurological injuries impacting pathophysiological events

Language: Английский

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Role of Cell Deaths in Human Disabilities

Published: Jan. 1, 2025

Language: Английский

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Importance of AIM2 as a serum marker for reflecting severity and predicting a poor outcome of human severe traumatic brain injury: A prospective longitudinal cohort study

Clinica Chimica Acta, Journal Year: 2024, Volume and Issue: 559, P. 119691 - 119691

Published: April 27, 2024

Language: Английский

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer’s disease

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(6), P. 1644 - 1664

Published: July 10, 2024

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer’s disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation tau protein, an endogenous microtubule-associated protein protects integrity neuronal cytoskeletons. Tau results in misfolding subsequent accumulation tangles forming neurotoxic aggregates. These misfolded proteins characteristic can lead to downstream neuroinflammatory processes, including assembly activation inflammasome complex. Inflammasomes refer a family multimeric units that, upon activation, release cascade signaling molecules resulting caspase-induced cell death inflammation mediated by interleukin-1β cytokine. specific inflammasome, NOD-like receptor 3, has been proposed be key regulator phosphorylation where it shown prolonged 3 acts as causal factor pathological spreading. This review begins describing epidemiology pathophysiology disease. Next, we highlight overriding theme discuss role formation deposits how such tauopathic entities spread throughout brain. We then propose novel framework linking inflammasome-dependent pathologies exist along temporal continuum. Finally, potential therapeutic targets may intercept this pathway ultimately minimize long-term decline.

Language: Английский

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Analysis of miRNA Expression Profiles in Traumatic Brain Injury (TBI) and Their Correlation with Survival and Severity of Injury

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9539 - 9539

Published: Sept. 2, 2024

Traumatic brain injury (TBI) is the leading cause of traumatic death worldwide and a public health problem associated with high mortality morbidity rates, significant socioeconomic burden. The diagnosis may be difficult in some cases or leave diagnostic doubts, especially mild trauma insignificant pathological changes where instrumental tests are negative. Therefore, recent years, an important area research has been directed towards study new biomarkers, such as micro-RNAs (miRNAs), which can assist clinicians diagnosis, staging, prognostic evaluation TBI, well forensic pathologists assessment TBI estimation additional relevant data, survival time. aim this to investigate expression profiles (down- upregulation) panel miRNAs subjects deceased order assess, verify, define role played by non-coding RNA molecules different pathophysiological mechanisms damage. This also aims correlate detected time, defined time elapsed between event death, severity trauma. was conducted on 40 (study group) 10 suddenly from non-traumatic causes (control group). group stratified according selection examined based thorough literature review. Analyses were performed formalin-fixed, paraffin-embedded (FFPE) tissue samples, first step total extraction second quantification selected interest. showed higher levels compared controls for miR-16, miR-21, miR-130a, miR-155. In contrast, lower found miR-23a-3p. There no statistically differences miR-19a. short survival, miR-16-5p miR-21-5p significantly higher. long lower. miR-130a middle survival. relation severity, critical-fatal subgroup. Conclusions: provides evidence potential investigated predictive biomarkers discriminate controls. These could improve postmortem offer possibility analysis become key tool investigations, providing more precise detailed information nature extent helping circumstances death.

Language: Английский

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High fat diet exacerbates long-term metabolic, neuropathological, and behavioral derangements in an experimental mouse model of traumatic brain injury

Life Sciences, Journal Year: 2022, Volume and Issue: 314, P. 121316 - 121316

Published: Dec. 22, 2022

Language: Английский

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