Zipper-interacting protein kinase mediates neuronal cell death and cognitive dysfunction in traumatic brain injury via regulating DEDD

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Март 4, 2025

Abstract Neuronal cell death is a causative process in traumatic brain injury (TBI)-induced structural and functional impairment of the central nervous system. However, upstream trigger TBI-induced neuronal loss underlying molecular pathways remain unclear. Zipper-interacting protein kinase (ZIPK) has been shown to be upregulated Alzheimer’s disease ischemic stroke play role cellular apoptosis, while its pathological significance TBI not reported. Herein, we discovered for first time that ZIPK expression was markedly elevated neurons after caused massive apoptosis peri-contusional regions. Zipk haploinsufficiency antagonized reversed several typical neuropathological changes induced by TBI. Mechanistically, found affected viability modulating effector domain-containing DNA binding (DEDD) caspase-3 pathway. Specifically, could bind phosphorylate DEDD at S9 residue, thus enhancing stability DEDD, leading activation caspase-3-mediated apoptotic cascade neurons. The rescue downregulation effectively alleviated behavioral deficits preserving motor cognitive abilities vivo, supporting decisive dysregulation TBI-associated dysfunctions survival. Furthermore, pharmacological suppression activity specific inhibitor prior protected from injury-induced degeneration vitro vivo preventing upregulation activation. In conclusion, our data reveal essential contribution through DEDD/caspase-3 cascade, suggest potential targeting as an effective strategy treating TBI-related neuropathologies.

Язык: Английский

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A Self‐Gelling Powder Directly Co‐Assembled by Natural Small Molecules for Traumatic Brain Injury

Advanced Functional Materials, Год журнала: 2024, Номер 34(29)

Опубликована: Март 14, 2024

Abstract The prognosis for traumatic brain injury (TBI) depends largely on prompt hemostasis and effective pharmacologic interventions. Natural all‐small‐molecule self‐gelling powder, integrating the advantages of self‐assembled small‐molecule hydrogels powders, is expected to provide timely prehospital management TBI. However, synthesis application natural powder still uncharted territory. In this study, an co‐assembled MGF‐H 3 BO ‐RUT (MBR) fabricated through co‐assembly mangiferin (MGF) rutin (RUT) in H /NaOH aqueous solution. Both compounds can bind with boric acid, leading co‐assembling into hydrogen‐bonding interactions π – stacking. MBR then obtained by drying as‐prepared hydrogels, thus pharmacodynamics one. Remarkably, it displays robust regeneration capabilities, while retaining excellent self‐healing properties injectability after drying‐hydration cycles. Moreover, not only achieves rapid but also attenuates conspicuously cerebral edema inflammatory response TBI situ spraying, exhibiting notable neuroprotective effects without discernible toxic side effects. This study provides a novel assembly strategy form gel materials originating from small molecules, offering promising avenues treatment acute phase.

Язык: Английский

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Small Molecule Hydrogels Loading Small Molecule Drugs from Chinese Medicine for the Enhanced Treatment of Traumatic Brain Injury

ACS Nano, Год журнала: 2024, Номер 18(42), С. 28894 - 28909

Опубликована: Окт. 9, 2024

Self-assembly of hydrogels for mechanical support and drug delivery has been extensively researched in traumatic brain injury (TBI), where treatment options are limited. The chief challenge is that most self-assembled rely on high molecular carriers or the incorporation exogenous inactive substances as mediators. It difficult these systems to achieve clinical translation due concerns regarding biological safety. Here we report a small molecule hydrogel (GBR-gel) loading drugs (glycyrrhizic acid, berberine, rhein) originated from popular Chinese medicines without additional components under physiological conditions. In long run, GBR-gel possesses several advantages, including ease preparation, cost-effectiveness, biocompatibility. As proof-of-concept, allows prompt administration at site exert potent pharmacodynamic effects. Further single-cell RNA sequencing experimental validation indicated can effectively rescue suppressed glutamatergic synapse pathway after TBI, thereby attenuating inflammatory responses neural impairments. Our work provides an alternative strategy timely intervention TBI.

Язык: Английский

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Impact of mild traumatic brain injury on health behaviors

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 10, 2025

Health-related behavioral changes may occur following traumatic brain injury. We focused on understanding the impact of mild injury (TBI) health-related behaviors and identifying factors associated with such changes. utilized health check-up records from Korean National Health Insurance Service database spanning January 1, 2009, to December 31, 2017. The sample included 49,212 patients diagnosed TBI 1:1 matched controls who participated in national check-ups 2009–2010, 2011–2012, 2016–2017. Multivariable logistic regression analysis was examine association between short- long-term Mild significantly an increased risk insufficient physical activity at [odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01 − 1.07] (OR, 1.06; CI, 1.03 1.09) follow-ups. Age ≥ 65 years female sex were significant effect modifiers for 1.11; 1.02 1.21) smoking 1.31; 1.14 1.51), respectively. lead detrimental changes, varying by age sex. Thus, age- sex-specific interventions be needed address these

Язык: Английский

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Aqueous Grown Quantum Dots with Robust Near-Infrared Fluorescence for Integrated Traumatic Brain Injury Diagnosis and Surgical Monitoring

ACS Nano, Год журнала: 2024, Номер 18(29), С. 19038 - 19053

Опубликована: Июль 9, 2024

Surgical intervention is the most common first-line treatment for severe traumatic brain injuries (TBIs) associated with high intracranial pressure, while complexity of these surgical procedures often results in complications. Surgeons struggle to comprehensively evaluate TBI status, making it difficult select optimal strategy. Here, we introduce a fluorescence imaging-based technology that uses high-quality silver indium selenide-based quantum dots (QDs) integrated diagnosis and guidance. These engineered, poly(ethylene glycol)-capped QDs emit near-infrared region, are resistant phagocytosis, importantly, ultrastable after epitaxial growth an aluminum-doped zinc sulfide shell aqueous phase renders long-term light irradiation complex physiological environments. We found intravenous injection enabled both precise mouse model and, more comprehensive evaluation status before, during, operation distinguish from superficial hemorrhages, provide real-time monitoring secondary hemorrhage, guide decision on evacuation hematomas. This QD-based diagnostic system could ultimately complement existing clinical tools treating TBI, which may help surgeons improve patient outcomes avoid unnecessary procedures.

Язык: Английский

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An innovative and mass-sensitive Quartz Tuning Fork (QTF) biosensor for GFAP detection: A novel approach for Traumatic Brain Injury diagnosis

Biosensors and Bioelectronics X, Год журнала: 2025, Номер unknown, С. 100614 - 100614

Опубликована: Март 1, 2025

Язык: Английский

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Poor long-term outcomes and abnormal neurodegeneration biomarkers after military traumatic brain injury: the ADVANCE study

Journal of Neurology Neurosurgery & Psychiatry, Год журнала: 2024, Номер unknown, С. jnnp - 333777

Опубликована: Окт. 11, 2024

Background Traumatic brain injury (TBI) is common in military campaigns and a risk factor for dementia. A rme D Ser V ices Tr uma Rehabilitatio N Out C om E -TBI (ADVANCE-TBI) aims to ascertain neurological outcomes UK personnel with major battlefield trauma, leveraging advances quantification of axonal breakdown markers like neurofilament light (NfL), astroglial marker glial fibrillar acidic protein (GFAP) blood. We aimed describe the causes, prevalence consequences TBI, its fluid biomarker associations. Methods TBI history was ascertained 1145 servicemen veterans, whom 579 had been exposed trauma. Functional mental health assessments were administered, blood samples collected approximately 8 years postinjury, plasma biomarkers quantified (n=1125) NfL, GFAP, total tau, phospho-tau 181 , amyloid-β 42 40. Outcomes related neurotrauma exposure. Results present 16.9% (n=98) participants, 46.9% classified as mild-probable 53.1% moderate severe. Depression (β=1.65, 95% CI (1.33 2.03)), anxiety (β=1.65 (1.34 2.03)) post-traumatic stress disorder (β=1.30 (1.19 1.41)) symptoms more after alongside poorer 6 minute walk distance (β=0.79 (0.74 0.84)) quality life (β=1.27 1.36), all p<0.001). Plasma GFAP 11% (95% 2 21) higher post-TBI (p=0.013), greater concentrations moderate-to-severe injuries (47% than 20% 82%, Unemployment among those elevated levels post-TBI, showing 1.14-fold increase 1.03 1.27, p<0.001) every doubling concentration. Conclusions affected nearly fifth trauma-exposed personnel, worse health, motor functional outcomes, well post-injury. This absent extracranial showed dose-response relationship severity injury.

Язык: Английский

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Traumatic Brain Injury and Risk of Incident Comorbidities

JAMA Network Open, Год журнала: 2024, Номер 7(12), С. e2450499 - e2450499

Опубликована: Дек. 12, 2024

Importance Traumatic brain injury (TBI) is associated with chronic medical conditions. Evidence from diverse clinical administrative datasets may improve care delivery. Objective To characterize post-TBI risk of incident neuropsychiatric and conditions in a California health system database validate findings Massachusetts dataset. Design, Setting, Participants In this cohort study, prospective longitudinal cohorts using data 5 University settings between 2013 2022 were studied. Patients aged 18 years older mild (mTBI) or moderate to severe TBI (msTBI) included. Unexposed individuals propensity matched by age, race ethnicity, sex, site, insurance coverage, area deprivation index (ADI) score, duration date most recent encounter. study comorbidities interest before the excluded. Data analyzed August October 2024. Exposure TBI. Main Outcomes Measures International Classification Diseases, Ninth Revision ( ICD-9 ) Statistical Tenth Revision, Clinical Modification ICD-10-CM codes used identify patients up 22 within neurological, psychiatric, cardiovascular, endocrine umbrella groupings. Cox proportional hazard models generate yearly ratios (HRs) 6 months 10 after Models further stratified age ADI score. Results The consisted 20 400 (9264 female [45.4%]; 1576 Black [7.7%], 3944 Latinx [19.3%], 480 White [51.4%]), including 5100 mTBI (median [IQR] 36.0 [25.0-51.0] years), msTBI [IQR 35.0 [25.0-52.0] 200 control group years). By score quintile, there 2757 unexposed (27.0%), 1561 (30.6%), 1550 (30.4%) lowest (1-2) quintiles 1523 (14.9%), 769 (15.1%), 804 (15.8%) highest (9-10). any severity was increased nearly all (mTBI HRs ranged 1.30; 95% CI, 1.07-1.57 for hypothyroidism 4.06; 3.06-5.39 dementia, 1.35; 1.12-1.62 3.45; 2.73-4.35 seizure disorder). Separate stratifications revealed patient populations at risk, middle-age adults (ages 41-60 suicidality (mTBI: HR, 4.84; 3.01-7.78; msTBI: 4.08; 2.51-6.62). Suicidality persisted high subgroup (HR, 2.23; 1.36-3.66). Conclusions Relevance factor treatable other conditions, validating similar Additional exploratory suggested varying demographic regional patterns, which causal hypotheses research inform surveillance strategies.

Язык: Английский

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A Transdiagnostic, Hierarchical Taxonomy of Psychopathology Following Traumatic Brain Injury (HiTOP-TBI)

Journal of Neurotrauma, Год журнала: 2024, Номер unknown

Опубликована: Июль 6, 2024

Psychopathology, including depression, anxiety, and post-traumatic stress, is a significant yet inadequately addressed feature of moderate-severe traumatic brain injury (TBI). Progress in understanding treating post-TBI psychopathology may be hindered by limitations associated with conventional diagnostic approaches, specifically the

Язык: Английский

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Social deficits mirror delayed cerebrovascular dysfunction after traumatic brain injury

Acta Neuropathologica Communications, Год журнала: 2024, Номер 12(1)

Опубликована: Авг. 7, 2024

Abstract Traumatic brain injury (TBI) survivors face debilitating long-term psychosocial consequences, including social isolation and depression. TBI modifies neurovascular physiology behavior but the chronic physiological implications of altered perfusion on interactions are unknown. Adult C57/BL6 male mice received a moderate cortical TBI, behaviors were assessed at baseline, 3-, 7-, 14-, 30-, 60-days post (dpi). Magnetic resonance imaging (MRI, 9.4T) using dynamic susceptibility contrast weighted MRI acquired. At 60dpi underwent histological angioarchitectural mapping. Analysis utilized standardized protocols followed by cross-correlation metrics. Social deficits emerged as reduced with familiar cage-mate (partner) that mirrored significant reductions in cerebral blood flow (CBF) 60dpi. CBF perturbations temporally across regions known to regulate such hippocampus, hypothalamus, rhinal cortex. TBI-mice decline preference spend time cage mate. Cortical vascular density was also corroborating interactions. Thus, late emergence interaction be involved behaviors. Vascular morphology function improved prior decrements our correlations strongly implicate linkage between density, perfusion, Our study provides clinically relevant timeline alterations alongside functional recovery can guide future therapeutics.

Язык: Английский

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