Background Traumatic brain injury (TBI) results in permanent neurological deficits, with apoptosis critically affecting outcomes. The Bax/Bcl‐2 pathway–associated mitochondrial apoptosis is a key intrinsic death cascade. Mitophagy is implicated in TBI pathology; however, whether melatonin can regulate Bax/Bcl‐2 pathway–associated apoptosis through mitophagy remains unclear. Methods In vitro and in vivo TBI models were established using HT22 cells subjected to oxygen‐glucose deprivation/reoxygenation and the Feeney weight‐drop mouse model, respectively. Mitophagy was evaluated by measuring changes in LC3B, p62, COX IV, and TOM20 levels via western blotting in both models. In addition, mitochondrial ultrastructure was examined by transmission electron microscopy in vitro, and LC3B/TOM20 and TOM20/LAMP2 colocalization was evaluated by immunofluorescence in vivo. Moreover, Bax and Bcl‐2 expression was detected by western blotting. Apoptosis was evaluated by flow cytometry in vitro and TUNEL staining in vivo. Results TBI enhanced mitophagy, increased the Bax/Bcl‐2 ratio, and augmented apoptosis. Pharmacological inhibition of mitophagy with Cyclosporine A (CsA) further upregulated Bax, downregulated Bcl‐2, and exacerbated apoptotic cell death. Melatonin treatment significantly enhanced mitophagy in both models, leading to a reduced Bax/Bcl‐2 ratio and attenuated apoptosis. Notably, the antiapoptotic effects of melatonin were attenuated by coadministration of CsA, suggesting that its protective action is at least partially mediated by enhanced mitophagy. Conclusion Melatonin attenuates TBI‐induced apoptosis at least in part through enhanced mitophagy, which in turn suppresses the Bax/Bcl‐2 pathway–associated mitochondrial apoptosis. These findings suggest that the mitophagy‐Bax/Bcl‐2 axis may represent a promising therapeutic target, and melatonin warrants further investigation as a potential candidate for TBI treatment.
Background Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that often impairs quality of life (QoL). Although psychological resilience may facilitate adaptation to MS, the interaction between psychological and neurological features of MS patients remains unclear. The objective of the present study is to investigate the association between psychological resilience, QoL, disability and structural brain MRI measures in young adults with early MS. Methods Forty‐six patients aged 18–45 years with a diagnosis of MS within the last 2 years were assessed. Resilience was measured using the Connor–Davidson Resilience Scale (CD‐RISC25) and QoL using the Multiple Sclerosis Quality of Life‐54 (MSQoL‐54). MRI measures included normalized brain, white matter, and gray matter volumes, and T2 lesion volume (T2LV). Disability was assessed with the Expanded Disability Status Scale (EDSS). Associations were examined using Pearson′s or Spearman′s coefficients as appropriate. Results Psychological resilience and QoL were not associated with MRI measures or disability. Physical QoL was inversely correlated with EDSS score (rho = −0.48, p < 0.001). Conclusion In early MS, psychological variables appear independent of structural disease burden and disability, whereas physical QoL is associated with clinical disability. These findings support a biopsychosocial model suggesting that psychological adaptation of MS patients is influenced by complex mechanisms reaching beyond conventional MRI measures of structural damage.
ObjectiveBiomarkers that can distinguish motor neuron disease spectrum conditions, such as spinal and bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS), could facilitate early-stage diagnosis. This study used a multibiomarker approach to improve the differential diagnosis between SBMA and ALS.MethodsIn this study, plasma samples were collected from patients with SBMA (n = 44), male patients with ALS (n = 26), and healthy controls (n = 20). Plasma levels of neurofilament light chain (NfL), creatine (Cr), and Cr kinase (CK) were measured. Disease severity was assessed using the Revised ALS Functional Rating Scale scores and its subscores in both patient groups. Additionally, SBMA-specific functional measures, including SBMA Functional Rating Scale (SBMAFRS) scores and the 6-Min Walk Test (6MWT), were evaluated in patients with SBMA.ResultsNfL levels were significantly higher in patients with ALS than in patients with SBMA and healthy controls, and were significantly influenced by age. When the three biomarkers were entered into logistic regression models, NfL levels alone could be used to differentiate ALS from SBMA almost perfectly, and the inclusion of Cr or CK levels did not improve this differentiation. Within the SBMA group, however, Cr levels were correlated with the lower-limb subscore of the SBMAFRS and with 6MWT results, which points to a role in tracking motor function rather than in diagnosis.ConclusionsOur results indicated that plasma NfL levels could be used to reliably distinguish ALS from SBMA, whereas plasma Cr levels were better suited as a marker of muscle function and disease severity in SBMA. Measuring both of these may therefore aid diagnosis as well as prognostic assessment in patients with suspected motor neuron disease.
Background: Low-intensity transcranial ultrasound stimulation (TUS) is an advanced noninvasive neuromodulation technique with great clinical potential. The hippocampal cornu ammonis 1 (CA1) is a crucial subfield for higher cognitive functions, such as memory formation, and is integrally involved in sleep-dependent memory consolidation. Objectives: This study sought to establish computational models for low-intensity TUS targeting the bilateral CA1 and to analyze the simulation parameters. Methods: We recruited eight young adults (mean age: 25.75 years) and 10 cognitively unimpaired older adults (mean age: 68.98 years). Based on T1-weighted magnetic resonance imaging (MRI) data, bilateral CA1 volumes were segmented and quantified for target localization. We constructed a simulation model on the k-Plan platform for low-intensity TUS delivered to the bilateral CA1 through the lateral pathway. Hemispheric-specific focal distance, spatial-peak pulse-average intensity (ISPPA), maximum temperature change (Delta T), and mechanical index (MI) were compared between age groups. Results: Compared with young adults, older adults showed significantly shorter focal distance (t = 3.61, p = 0.003), higher in situ ISPPA (t = -4.38, p = 0.001), higher maximum Delta T (t = -6.50, p < 0.001), and higher MI (t = -3.40, p = 0.008) induced by low-intensity TUS targeting right CA1. A significant hemispheric difference in focal distance was observed exclusively in older adults, with the left CA1 exhibiting a longer focal distance than the right side (t = 2.34, p = 0.044). Correlation analyses incorporating volumetric data further revealed different age-related patterns across two age groups. Conclusion: This study evaluates the age- and hemisphere-related differences in low-intensity TUS simulations targeting the bilateral CA1 in young and older adults. These findings provide important guidance for the clinical translation of low-intensity TUS in the aging population and the development of personalized therapeutic protocols.
IntroductionIschemic stroke is a major global cause of disability and death. Although clot-removing endovascular treatment (EVT) is the standard treatment for large vessel occlusion, the additional benefit of permanent intracranial stenting during EVT remains uncertain. This study is aimed at comparing outcomes between patients treated with EVT alone and those who also received a permanent stent, focusing on a predominantly Caucasian population.Patients and methodsWe analyzed data from 14,435 stroke patients treated with EVT across 16 comprehensive stroke centers in the EVA-TRISP collaboration. Among them, 386 patients received a permanent intracranial stent. Functional outcomes at 3 months and the occurrence of fatal and symptomatic intracerebral hemorrhage (ICH) were evaluated using ECASS II/III criteria.ResultsStent placement was not initially associated with worse functional outcome in univariable analysis (OR 1.19, 95% CI 0.98-1.43). However, stent placement was associated with worse prognosis after adjusting for age, sex, comorbidities, and Prior IV thrombolysis (OR 1.36, 95% CI 1.13-1.67). There were no significant differences in symptomatic, fatal ICH or 3-month mortality between the groups.DiscussionPatients treated with EVT alone had better functional recovery and less disability at 3 months. However, the reason for stenting was not documented for this cohort.ConclusionIn this multicenter cohort, EVT alone was associated with better functional outcomes than EVT with stenting. Further randomized studies are needed to identify patients who may benefit from stenting.
