Brain Research Bulletin最新文献

{"title":"HSP47 inhibitor Col003 inhibits glial scar formation and improves neurological function in ischemic stroke in rats","authors":"Kejian Zhou ,&nbsp;Yuliang Xie ,&nbsp;Xiaoyun Xie,&nbsp;Haoying Li,&nbsp;Tingting Liang,&nbsp;Jinpin Li,&nbsp;Jingli Liu","doi":"10.1016/j.brainresbull.2026.111745","DOIUrl":"10.1016/j.brainresbull.2026.111745","url":null,"abstract":"<div><h3>Background</h3><div>Glial scarring is a major obstacle for axonal regeneration and neural repair in the late stage of ischemic stroke. Reactive astrocytes are the main component of the glial scar. Heat shock protein 47 (HSP47) is significantly expressed in reactive astrocytes and remains present in the glial scar. However, the role of HSP47 in glial scar formation in ischemic stroke remains unclear.</div></div><div><h3>Methods</h3><div>HSP47 was identified in the peri-infarct region of rats at 1, 7, and 14 days post middle cerebral artery occlusion (MCAO). The rats received daily tail vein injections of the HSP47 inhibitor Col003 from days 1–14 following MCAO. Glial scar, brain atrophy volume, neurological score was detected after ischemia.</div></div><div><h3>Results</h3><div>HSP47 levels were increased in the peri-infarct area at 1, 7, and 14 days post-MCAO, as did those in astrocytes subjected to oxygen<img>glucose deprivation/reoxygenation (OGD/R). The HSP47 inhibitor Col003 enhanced neurological functional recovery and minimized glial scar formation. Col003 inhibited the proliferation and migration of OGD/R-induced astrocytes and reduced the expression of glial fibrillary acidic protein, neurocan, and phosphacan. RNA-seq analysis revealed that differentially expressed genes in the Col003 treatment group were enriched in the JAK2/STAT3 pathway, which is associated with astrogliosis and glial scar formation.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrated that Col003 inhibited JAK2/STAT3 phosphorylation in OGD/R-induced astrocytes. The HSP47 inhibitor Col003 might suppress astrocyte proliferation, migration, and glial scar formation through the JAK2/STAT3 pathway following ischemic stroke, which suggests a novel therapeutic strategy for the chronic phase of ischemic stroke.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"236 ","pages":"Article 111745"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of whole-brain network topology and weighted gene coexpression analysis to identify potential imaging and molecular markers for glioma grading","authors":"Yue Yuan,&nbsp;Xun-Heng Wang","doi":"10.1016/j.brainresbull.2026.111765","DOIUrl":"10.1016/j.brainresbull.2026.111765","url":null,"abstract":"<div><h3>Background</h3><div>Glioblastoma (GBM), which is characterized by high invasiveness and spatial heterogeneity, poses significant challenges in terms of prognosis and treatment. In this study, whole-brain network topology was combined with gene coexpression analysis to identify potential imaging and molecular markers for glioma grading, shifting the research focus from localized tumor lesions to the interaction mechanisms between the nervous system and gliomas.</div></div><div><h3>Methods</h3><div>In this study, data from open-access datasets, including glioma imaging data from the Brain Tumor Segmentation Challenge (BraTS’2019), data on glioma-related genes from BrainBase, and whole-brain transcriptomic data from the Allen Human Brain Atlas, were used. Wavelet-based features were extracted separately from T1- and T2-weighted magnetic resonance (MR) images and integrated to construct individualized structural brain networks with the aim of characterizing glioma heterogeneity. LASSO regression was applied to perform feature selection and extract the representative structural network metrics. We evaluated the effectiveness of the derived network features in glioma grading from this novel perspective via four classification models: support vector machine (SVM), random forest, logistic regression, and XGBoost. Furthermore, weighted gene coexpression network analysis (WGCNA) was employed to link disruptions in structural connectivity between high- and low-grade gliomas with the expression patterns of glioma-related genes, thereby identifying potential molecular markers associated with tumor progression.</div></div><div><h3>Results</h3><div>The results demonstrated that the whole-brain network-based grading approach achieved test-set AUC values above 0.85 across all four models, with the SVM and logistic regression models showing the best performance (AUC = 0.87). Additionally, the high invasiveness of high-grade gliomas may lead to the decoupling and reorganization of structural network modules. Protein kinase C beta (PRKCB) has been identified as a potential molecular biomarker associated with glioma grade.</div></div><div><h3>Conclusions</h3><div>Wavelet-based individualized brain structural networks have been proposed for glioma grading models, resulting in novel imaging and molecular markers for cancer neuroscience.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"236 ","pages":"Article 111765"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orexin dual receptor antagonist attenuates neurological deficits possibly via PI3K/Akt/mTOR pathway activation in sleep-deprived stroke rats","authors":"Lili Wang ,&nbsp;Xinli Xiong ,&nbsp;Baofeng Wang ,&nbsp;Haiyu Li ,&nbsp;Gang Li ,&nbsp;Feifeng Liu","doi":"10.1016/j.brainresbull.2026.111762","DOIUrl":"10.1016/j.brainresbull.2026.111762","url":null,"abstract":"<div><h3>Background</h3><div>Post-stroke sleep disorders are frequent complications of ischemic stroke and contribute to poor neurological recovery. Dual orexin receptor antagonists (DORAs) promote sleep via mechanisms distinct from traditional hypnotics. This study investigated whether almorexant attenuates sleep deprivation (SD)-aggravated ischemic injury in rats and explored the its potential association with PI3K/Akt/mTOR signaling pathway.</div></div><div><h3>Methods</h3><div>Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO), and were assigned to sham, MCAO, MCAO+SD, MCAO+SD+almorexant, or MCAO+SD+estazolam. Neurological function (Zea-Longa score, open-field test), infarct volume (TTC), histopathology (H&amp;E), neuronal apoptosis (TUNEL), and PI3K/Akt/mTOR expression (Western blot, RT-qPCR) were assessed.</div></div><div><h3>Results</h3><div>SD exacerbated neurological deficits after MCAO, as reflected by higher Zea–Longa scores and impaired locomotor activity. Almorexant treatment was associated with improved behavioral performance and reduced histologic injury, neuronal apoptosis in sleep-deprived MCAO rats. At the molecular level, both almorexant and estazolam treatments were associated with upregulated PI3K, Akt, and mTOR expression at both protein and mRNA levels.</div></div><div><h3>Conclusion</h3><div>Almorexant was associated with attenuation of SD-exacerbated ischemic brain injury in rats, accompanied by alterations in PI3K/Akt/mTOR signaling, suggesting DORAs may have potential relevance for the management of post-stroke insomnia.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"236 ","pages":"Article 111762"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning-based one-stop 11C-CFT and 18F-FDG dual-tracer brain PET imaging protocol for Parkinson’s disease","authors":"Xiaolin Sun ,&nbsp;Yuan Chang ,&nbsp;Xiaoyue Tan ,&nbsp;Qing Zhang ,&nbsp;Hao Sun ,&nbsp;Shanzhen He ,&nbsp;Fanghu Wang ,&nbsp;Lijun Lu ,&nbsp;Lei Jiang","doi":"10.1016/j.brainresbull.2026.111764","DOIUrl":"10.1016/j.brainresbull.2026.111764","url":null,"abstract":"<div><div>This study explored using deep learning (DL) to separate short-interval staggered ¹¹C-CFT/¹⁸F-FDG brain PET images for Parkinson’s disease, aiming to reduce scan waiting time. A total of 67 patients performing ¹¹C-CFT and ¹⁸F-FDG brain PET scans on separate days were retrospectively enrolled. A Swin UNETR model was trained to generate pseudo ¹⁸F-FDG PET images from simulated dual-tracer sum images. The simulation assumed ¹⁸F-FDG was administered at 80, 100, 120, or 200 min (∆t) after ¹¹C-CFT injection. Compared to actual ¹⁸F-FDG images, the pseudo images showed high visual similarity across all ∆t intervals. Low average NMSE values (∼0.0004) and high average SSIM values (0.9991–0.9993) were consistently achieved across all Δt groups. Bland &amp; Altman analysis of the whole brain region demonstrated low average SUVR bias across all Δt groups remained within ±0.001. Region-wise correlation analysis revealed strong correlations between actual and pseudo ¹⁸F-FDG images across all Δt, with slopes ranging from 0.994 to 1.001, and all R²&gt; 0.99. SUVmean, LBR and SNR values for pseudo ¹⁸F-FDG images exhibited no statistically significant differences compared to actual ¹⁸F-FDG images (<em>P</em> &gt; 0.05). Dual-tracer PET images can be effectively separated using the DL model, yielding high-quality visual and semi-quantitative results when ¹⁸F-FDG is injected immediately after the ¹¹C-CFT PET scan, thereby reducing patient wait time, improving patient comfort, and enhancing overall clinical efficiency.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"236 ","pages":"Article 111764"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain complexity in motion: Multiscale entropy analysis on mobile EEG data to assess motor performance","authors":"Daghan Piskin ,&nbsp;Gjergji Cobani ,&nbsp;Daniel Büchel ,&nbsp;Tim Lehmann ,&nbsp;Jochen Baumeister","doi":"10.1016/j.brainresbull.2026.111769","DOIUrl":"10.1016/j.brainresbull.2026.111769","url":null,"abstract":"<div><div>Multiscale entropy (MSE) as a measure of brain complexity provides substantial insights into the adaptability of the brain. However, it is often applied to resting-state electroencephalography (EEG) or in static tasks. The current study assessed the reliability, validity and classification accuracy of MSE computed on mobile EEG data for linking brain complexity to motor performance within a kicking task. Eleven novice participants underwent repeated measurements to assess test-retest reliability, while the data from 15 novices and 15 football players were used to evaluate known-groups validity, convergent validity and classification accuracy. EEG data were recorded using 65 active electrodes and MSE estimates were computed for 64 time scales on preprocessed data. Results showed poor to excellent reliability for MSE estimates, exhibiting channel- and scale-specific variations, with reliability generally higher at fine-to-mid scales. Experts exhibited significantly lower entropy at coarse scales in left frontal and at fine scales in centroparietal regions compared to novices. Negative correlations were found between entropy estimates and kicking accuracy. Receiver operating characteristic curves of entropy estimates and their principal components demonstrated moderate to good classification accuracy between expertise levels. These findings suggest MSE as a promising metric for investigating brain complexity in movement contexts, revealing distinct patterns of complexity associated with motor performance. Future research across diverse tasks and populations is crucial to further elucidate this relationship and explore the applied potential of MSE.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"236 ","pages":"Article 111769"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential roles of metabolomic alterations in neuropathic pain: Evidence from In Vivo to clinical studies","authors":"Rattanaporn Khrueamun ,&nbsp;Chanisa Thonusin ,&nbsp;Nipon Chattipakorn ,&nbsp;Siriporn Chattipakorn","doi":"10.1016/j.brainresbull.2026.111754","DOIUrl":"10.1016/j.brainresbull.2026.111754","url":null,"abstract":"<div><div>Neuropathic pain is a chronic condition often associated with damage to the somatosensory nervous system. The exact mechanistic understanding of neuropathic pain remains elusive. Metabolomics, an analytical approach used to assess metabolic alterations in various diseases, is a promising technique that can offer mechanistic insights into neuropathic pain. It may lead to the identification of novel therapeutic targets and biomarkers. Evidence from animal studies indicates that alterations in multiple metabolic pathways, including those involving amino acids, fatty acids, glycolysis intermediates, Krebs cycle metabolites, and eicosanoids, have been observed in models of neuropathic pain. Changes in several metabolites, including phosphatidylcholine, arachidonic acid derivatives, and amino acid levels, have also been found in models of neuropathic pain. These alterations have been associated with mitochondrial dysfunction, impaired maintenance of the myelin sheath, and increased pain signaling. In addition, clinical studies have demonstrated dysregulation of glutamate, choline, phospholipid, and glucose metabolism in patients with neuropathic pain. These metabolic disturbances contribute to neuronal hyperexcitability and persistent pain. Interestingly, modulation of specific metabolic pathways has been shown to alleviate neuropathic pain, as evidenced by both <em>in vivo</em> and clinical studies. Therefore, this comprehensive review aims to summarize and discuss the metabolomic alterations associated with neuropathic pain.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"236 ","pages":"Article 111754"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subcortical regional volume vulnerability linked to child neglect without other forms of maltreatment","authors":"Natasha Y.S. Kawata ,&nbsp;Takashi X. Fujisawa ,&nbsp;Akiko Yao ,&nbsp;Hidehiko Okazawa ,&nbsp;Akemi Tomoda","doi":"10.1016/j.brainresbull.2026.111771","DOIUrl":"10.1016/j.brainresbull.2026.111771","url":null,"abstract":"<div><div>Child neglect during critical stages of development has been associated with long-term adverse outcomes, including impairments in social, emotional, and physical health, as well as elevated risks of mental and cardiovascular disorders. This study examined whether alterations in corpus callosum (CC) morphology—essential for interhemispheric communication—are associated with the neural mechanisms underlying psychosocial characteristics in children exposed to neglect. Brain morphology was assessed using T1-weighted magnetic resonance imaging in Japanese children with a history of neglect (neglect group, <em>n</em> = 22) and compared with non-maltreated Japanese children (non-CM group, <em>n</em> = 66). Boys in the neglect group exhibited a greater volume in the middle anterior portion of the CC (CC2) than non-CM boys (<em>d</em> = 0.81, estimate = 208.38, <em>t</em> = 3.35, false discovery rate [FDR]-adjusted <em>p</em> = 0.01). Additionally, CC2 volume was positively correlated with hyperactivity-inattention scores across both sexes (<em>d</em> = 0.53, estimate = 111.68, <em>t</em> = 2.85, FDR-adjusted <em>p</em> = 0.03). These findings indicate sex-specific effects of neglect on CC development and emphasize the importance of clarifying the neurodevelopmental consequences of neglect and their associations with psychosocial functioning.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"236 ","pages":"Article 111771"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture alleviates inflammatory pain via the activation of GABAergic inhibitory interneurons in mouse spinal dorsal horn","authors":"Jiawei Zhang ,&nbsp;Yang Bao ,&nbsp;Mengye Zhu ,&nbsp;Quan Wan ,&nbsp;Jinjin Zhang ,&nbsp;Xuezhong Cao ,&nbsp;Huan Zou ,&nbsp;Qinghua Yin ,&nbsp;Ziming Chen ,&nbsp;Gang Xu ,&nbsp;Xuexue Zhang ,&nbsp;Daying Zhang ,&nbsp;Tao Liu ,&nbsp;Yong Zhang","doi":"10.1016/j.brainresbull.2026.111741","DOIUrl":"10.1016/j.brainresbull.2026.111741","url":null,"abstract":"<div><div>Electroacupuncture (EA), a modern adaptation of traditional acupuncture, has shown promising analgesic effects across various pain models. However, the underlying central mechanisms remain insufficiently characterized. The dorsal horn of the spinal cord serves as a critical hub for the transmission and modulation of nociceptive signals. Increasing evidence suggests that spinal disinhibition, primarily resulting from impaired excitability of inhibitory interneurons and diminished synthesis or release γ-aminobutyric acid (GABA) and glycine, accounts for the development and maintenance of pain. In this study, we investigated whether EA alleviates inflammatory pain by modulating the activity of GABAergic inhibitory interneurons in the superficial dorsal horn of the spinal cord. A murine model of inflammatory pain was established by subcutaneous injection of complete Freund's adjuvant (CFA) into the hind paw. EA was applied at the Huantiao (GB30) and Yanglingquan (GB34) acupoints on alternate days following CFA injection. Mechanical hypersensitivity was assessed by paw withdrawal threshold. Neuronal activity was evaluated using immunofluorescence staining for c-fos, Lmx1b, Pax2, and GABA. Furthermore, whole-cell patch-clamp recordings were conducted on spinal slices from GAD67-GFP transgenic mice to assess the electrophysiological properties of GABAergic interneurons. EA significantly attenuated mechanical hypersensitivity in CFA-treated mice without affecting locomotor function. Immunofluorescence staining revealed that EA enhanced c-fos expression in the dorsal horn during early stages of treatment, reduced the proportion of c-fos-positive excitatory (Lmx1b-positive) neurons, and markedly increased the activation of inhibitory (Pax2-positive and GABA-positive) interneurons. In addition, electrophysiological recordings demonstrated that EA significantly depolarized the resting membrane potential and increased the firing frequency of GAD67-GFP-positive inhibitory interneurons in the CFA + EA group compared to the CFA group. Collectively, our results suggest EA at Huantiao and Yanglingquan acupoints could relieve inflammatory pain, potentially through enhancing of the excitability and activity of GABAergic inhibitory interneurons in the spinal dorsal horn. This study provides novel mechanistic insight into spinal modulation of nociceptive processing by EA and supports its therapeutic promise for inflammatory pain management.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111741"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saraswata Ghrita mitigates AlCl₃- and D-galactose–induced cognitive deficits in a murine Alzheimer’s-like model: In silico and in vivo insights","authors":"Robin Badal ,&nbsp;Balveer Kaur ,&nbsp;Harvinder Singh ,&nbsp;Poonam Sharma ,&nbsp;Pramod Yadav ,&nbsp;Arun Mahapatra ,&nbsp;Shivani Ghildiyal ,&nbsp;Ashok Kumar Patel ,&nbsp;Lalan Kumar ,&nbsp;Bhupesh Sharma ,&nbsp;Pradeep Kumar Prajapati ,&nbsp;Tanuja Nesari","doi":"10.1016/j.brainresbull.2026.111742","DOIUrl":"10.1016/j.brainresbull.2026.111742","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is characterized by cognitive decline linked to cholinergic dysfunction, oxidative stress, and neuroinflammation. Saraswata Ghrita (SG), a classical Ayurvedic formulation, was evaluated using an integrated in silico–in vivo workflow focusing on acetylcholinesterase (AChE) and related pathways.</div></div><div><h3>Methods</h3><div>SG constituents were profiled by GC–MS/MS and HR-LCMS/MS-QTOF. BBB-permeable, drug-like candidates were prioritized (SwissADME/BOILED-Egg) and evaluated by docking and molecular dynamics. In vivo, mice received AlCl₃ (4 mg/kg, i.p.) + <span>D</span>-galactose (50 mg/kg, i.p.) for 60 days; SG (3, 6, 12 mL/kg, p.o.) or donepezil (0.5 mg/kg, i.p.) was administered on days 31–60. Behavioral, biochemical, and histological endpoints were assessed (n = 6/group).</div></div><div><h3>Results</h3><div>In silico, LIG_91 showed the top predicted AChE binding affinity (−8.5 kcal·mol⁻¹) and LIG_212 scored −7.8 kcal·mol⁻¹ (supportive evidence). AlCl₃+<span>D</span>-galactose impaired cognition (MWM day-4 ELT 85.8 ± 5.3 s; TSTQ 34.6 ± 2.2 s). SG 12 mL/kg improved MWM performance (ELT 44.1 ± 3.2 s, ∼49 % lower vs model; TSTQ 50.1 ± 2.8 s, ∼45 %higher), while donepezil produced greater improvement (ELT 26.7 ± 2.4 s, ∼69 % lower; TSTQ 58.1 ± 5.4 s, ∼68 %higher). SG 12 mL/kg reduced oxidative stress (TBARS 12.93 ± 1.58 → 8.84 ± 0.52 nM/mg, ∼32 % decrease) and improved antioxidant status (GSH 7.52 ± 0.48 → 11.10 ± 0.48 µM/mg, ∼48 % increase). SG also attenuated neuroinflammation (IL-6 211.1 ± 10.6 → 165.0 ± 23.6 pg/mL, ∼22 % decrease; TNF-α 179.3 ± 8.7 → 133.7 ± 7.8 pg/mL, ∼25 % decrease; IL-10 12.3 ± 1.0 → 30.2 ± 5.2 pg/mL, ∼146 % increase) and lowered AChE activity (10.61 ± 0.61 → 8.49 ± 0.49 µM/min/mg, ∼20 % decrease). H&amp;E micrographs qualitatively suggested reduced cortical neuronal degeneration.</div></div><div><h3>Conclusions</h3><div>SG administration was associated with improved cognition and partial normalization of cholinergic, oxidative, and inflammatory markers in this model. Computational findings support possible AChE engagement but are not definitive; further quantitative histology and standardized-formulation studies are warranted.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111742"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircHIPK3 regulates TGF-β1/smad3 signaling in communicating hydrocephalus after intraventricular hemorrhage by sponging miR-30a-3p via ACT1","authors":"Yexin Yuan ,&nbsp;Qian Ouyang ,&nbsp;Yijian Yang ,&nbsp;Junqiang Wang ,&nbsp;Kaiyue Wang ,&nbsp;Peng Long ,&nbsp;Yifeng Chen ,&nbsp;Zhikun Liu ,&nbsp;Zhiping Zhang ,&nbsp;Zhangjie Su ,&nbsp;Gelei Xiao","doi":"10.1016/j.brainresbull.2026.111751","DOIUrl":"10.1016/j.brainresbull.2026.111751","url":null,"abstract":"<div><div>While circRNAs have been demonstrated to play critical roles in various neurological disorders, their functional mechanisms in post-intraventricular hemorrhage (IVH) communicating hydrocephalus remain poorly understood. Here we report a circular RNA, circular RNA homeodomain interacting protein kinase 3 (circHIPK3), significantly upregulated in meningeal tissues of IVH rat models. Knockdown of circHIPK3 markedly attenuated meningeal fibrosis, reduced ventricular dilation, and improved neurological function in IVH rats. Using both IVH rat models and thrombin-induced astrocyte cell lines, we validated the functional role of circHIPK3 in the pathogenesis of IVH-induced communicating hydrocephalus. Mechanistically, circHIPK3 functions as an endogenous sponge of miR-30a-3p to decrease its activity, resulting in upregulation of ACT1(TRAF3IP2) expression, which in turn triggers TGF-β1/Smad3 signaling pathway activation, ultimately driving fibrotic progression after IVH. Collectively, our findings suggest that circHIPK3 and its coupling mechanism are implicated in IVH, providing compelling evidence that circHIPK3 could be a key therapeutic target against post-IVH communicating hydrocephalus.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111751"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}