Brain Research Bulletin最新文献

{"title":"Expression of the extracellular matrix component brevican prior and after deep brain stimulation in the dtsz hamster model of dystonia","authors":"Anika Lüttig ,&nbsp;Stefanie Perl ,&nbsp;Denise Franz ,&nbsp;Malin Kotyra ,&nbsp;Markus Morawski ,&nbsp;Rüdiger Köhling ,&nbsp;Angelika Richter","doi":"10.1016/j.brainresbull.2025.111486","DOIUrl":"10.1016/j.brainresbull.2025.111486","url":null,"abstract":"<div><div>Maladaptive plasticity is thought to be involved in dystonia and paroxysmal dyskinesia, which often occur in early life in children and in animals. While the pathophysiology of these disorders is poorly understood, canine paroxysmal dyskinesia can be caused by a deletion in the gene, encoding the brain-specific component of the extracellular matrix (ECM) brevican (Brev). Brev plays a crucial role in the maturation of parvalbumin-reactive GABAergic interneurons (PV⁺). Therefore, in the present study we investigated whether abnormal expression of Brev coincides with age-dependent dystonia in the <em>dt</em>^<em>sz</em> hamster, a model of paroxysmal dystonia in which previous studies indicated altered maturation of striatal PV⁺. In addition, we examined if changes in Brev expression might be involved in antidystonic effects of deep brain stimulations (DBS) of the entopeduncular nucleus (EPN; analogue of the globus pallidus internus in primates). In comparison to age-matched non-dystonic control hamsters, <em>dt</em>^<em>sz</em> mutant hamsters showed a higher Brev expression in the ventral thalamic nucleus (21 and 35 days) and a lower number of Brev⁺ cells in the motor cortex (35 days). Furthermore, there were age-dependent differences especially a lower number of Brev⁺ cells in the motor cortex and a higher single cell intensity in the EPN (each in comparison to 21 and 90 days) at the age of 35 days (the age of maximum severity of dystonia). Brevican intensity seems to decrease at the age of 90 days (the age of spontaneous remission of dystonia) in some brain regions. EPN-DBS for 3 h was probably too short to induce significant changes as an explanation for recent electrophysiological data on cortico-striatal responses after DBS, but in sham-stimulated animal groups, the genotype-differences in motor cortex and thalamus could be confirmed. The present findings suggest that ECM warrant consideration in dystonia research.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111486"},"PeriodicalIF":3.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144748621","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":"Cognitive flexibility decline and right hemisphere's EEG alpha-band functional connectivity reorganization following repetitive indirect brain impacts in parachuters","authors":"Zhenghao Fu ,&nbsp;Kai Hu ,&nbsp;Shukai Wu ,&nbsp;Shuochen Wang ,&nbsp;Haoran Zhang ,&nbsp;Huanhuan Li ,&nbsp;Hang Xie ,&nbsp;Yukang Gong ,&nbsp;Guozheng Xu ,&nbsp;Jian Song","doi":"10.1016/j.brainresbull.2025.111485","DOIUrl":"10.1016/j.brainresbull.2025.111485","url":null,"abstract":"<div><div>The current study sought to investigate the relationship between cognitive flexibility and repetitive indirect brain impacts (RIBI) and to unravel the potential electrophysiological mechanism based on functional connectivity analysis. Forty-two male parachuters exposed to RIBI and 40 matched healthy controls (HC) were enrolled. Participants in the RIBI group had completed at least 40 actual jumps (46–106 times) and no less than 1000 simulated platform jumps (1000–4500 times). The RIBI group exhibited a significant increase in whole brain average time-frequency power within the alpha band, and a lower behavioral accuracy rate than the HC group. Spearman correlation revealed that the alpha band time-frequency power was negatively correlated with behavioral accuracy rates for both the repeat (r = -0.307, p = 0.048) and switch (r = -0.347, p = 0.024) conditions in the RIBI group. The RIBI group exhibited decreased alpha coherence (Coh) values predominantly noted between parietal and occipital regions in the right hemisphere, which indicate visual attention deficits in cognitive flexibility processing. Significantly increased alpha Coh values between frontal and parietal regions in the RIBI group, suggesting a compensatory brain response to cognitive flexibility impairment. Overall, this study provides robust evidence that the cumulative effects of RIBI can lead to a decline in cognitive flexibility. Additionally, enhanced frontoparietal and reduced parieto-occipital alpha functional connectivity in the right hemisphere reflects a unique adaptive reorganization of brain activity patterns following RIBI-induced cognitive flexibility impairment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111485"},"PeriodicalIF":3.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144748634","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":"Lutein ameliorates Parkinson's disease by regulating miR-135b-5p/SIRT1 to inhibit microglial M1 polarization and inflammation","authors":"Huai Huang ,&nbsp;Jiabin Duan ,&nbsp;Wenbin Duan ,&nbsp;Xiaomin Pu ,&nbsp;Changdi Ma ,&nbsp;Zhenghu Xu","doi":"10.1016/j.brainresbull.2025.111487","DOIUrl":"10.1016/j.brainresbull.2025.111487","url":null,"abstract":"<div><div>The development of Parkinson's disease (PD) is fundamentally linked to neuroinflammation and the overstimulation of microglia. Previous studies suggest that lutein exerts anti-inflammatory effects on the nervous system. This study aimed to investigate the function and mechanism of lutein in ameliorating PD. In this study, we experimentally explored an animal model of MPTP-induced PD and a model of lipopolysaccharide (LPS)-induced BV2 microglial inflammation. Behavioral tests, immunohistochemistry, and immunofluorescence were used to assess animal behavioral capacity and neuronal damage. Western blotting, RT<img>qPCR and ELISA were used to measure the levels of related proteins, genes and inflammatory factors. Dual-luciferase reporter gene assays and RIP detection were conducted to determine the relationship between miR-135b-5p and SIRT1. The results showed that lutein ameliorated behavior disorders and increased the number of TH-positive neurons in MPTP-induced PD mice. Lutein inhibited M1 polarization and inflammation in BV2 cells by decreasing the expression of the M1 markers iNOS and CD86 and the proinflammatory factors TNF-α, IL-β and IL-6 and increasing the expression of the M2 markers Arg-1 and CD206 and the anti-inflammatory factors IL-4 and IL-10. Lutein inhibited LPS-induced M1 polarization in BV2 cells by decreasing miR-30b-5p or activating SIRT1 expression, whereas miR-135b-5p negatively regulated SIRT1, and the knockdown of miR-135b-5p inhibited LPS-induced M1 polarization in BV2 cells by upregulating SIRT1. In conclusion, lutein upregulates SIRT1 expression by inhibiting miR-135b-5p, which in turn inhibits microglial M1 polarization and inflammation, thereby ameliorating PD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111487"},"PeriodicalIF":3.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752428","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":"Influences of current direction on 1 Hz motor cortex rTMS","authors":"Carolina Kanig ,&nbsp;Mirja Osnabruegge ,&nbsp;Florian Schwitzgebel ,&nbsp;Wolfgang Mack ,&nbsp;Martin Schecklmann ,&nbsp;Stefan Schoisswohl","doi":"10.1016/j.brainresbull.2025.111484","DOIUrl":"10.1016/j.brainresbull.2025.111484","url":null,"abstract":"<div><h3>Objective</h3><div>Neuromodulatory changes induced by repetitive transcranial magnetic stimulation (rTMS) are highly variable and lack replicability. Amongst many influencing factors, the current direction of the stimulation is known to affect rTMS aftereffects. In this study, we investigated the influence of current direction on cortical and peripheral markers of motor cortex plasticity as induced by 1 Hz rTMS as well as the correlation of cortical and peripheral markers. Additionally, we investigated possible confounding variables.</div></div><div><h3>Methods</h3><div>Twenty-five healthy subjects received 2000 pulses of 1 Hz rTMS at 110 % resting motor threshold intensity over the left motor hotspot inducing anterior-posterior – posterior-anterior (AP-PA) and posterior-anterior – anterior-posterior (PA-AP) current directions in the brain. Motor evoked potentials (MEPs) and transcranial evoked potentials (TEPs) before and after rTMS were assessed with single pulses. Coil placement was ensured by a neuronavigated robot-assisted setup.</div></div><div><h3>Results</h3><div>In sum, 1 Hz rTMS resulted in higher amplitudes of MEPs and TEP components N15, N45 and P60 and a reduced amplitude of N100, whereby the induced PA-AP current direction in the brain elicited higher effects. MEP and TEP N15 latency were prolonged and N100 shortened after rTMS. PA-AP current direction elicited stronger changes in latency for MEPs and N15. N45 and MEP correlated in the PA-AP pre rTMS condition with negligible effect size.</div></div><div><h3>Conclusions</h3><div>Our findings of facilitatory pre-to-post rTMS changes are in contrast to preliminary assumptions that 1 Hz rTMS acts inhibitory. However, since high variability and low reliability of rTMS aftereffects are prominent in the current literature, these results shed light that potential influencing factors need to be better reported, controlled and investigated. We suggest to further investigate effects of stimulation intensity and tiredness of subjects on rTMS. We were able to replicate current direction effects which strengthens the hypothesis of activation of different sets of neurons.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111484"},"PeriodicalIF":3.7,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741269","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":"Stem cell derived extracellular vesicles therapy for perinatal brain injury: A systematic review & meta-analysis of preclinical studies and a potential path to clinic","authors":"Xiaolin Guo ,&nbsp;Tingting Peng ,&nbsp;Mengru Zhong ,&nbsp;Simian Cai ,&nbsp;Lu He ,&nbsp;Kaishou Xu","doi":"10.1016/j.brainresbull.2025.111481","DOIUrl":"10.1016/j.brainresbull.2025.111481","url":null,"abstract":"<div><h3>Background</h3><div>Perinatal brain injury (PBI) is a significant cause of neonatal death and childhood disability. Current treatments for PBI are limited and ineffective. Stem cell derived extracellular vesicles (SC-EVs) have shown promising therapeutic potential in addressing PBI. We aimed to assess the effectiveness and potential mechanisms of SC-EVs therapy on behavioral and pathological outcomes in animal models of PBI.</div></div><div><h3>Methods</h3><div>We searched six databases (MEDLINE, Embase, Scopus, PubMed, ProQuest, and Web of Science) for articles on the therapeutic effects of SC-EVs in animal models of PBI. We extracted neurobehavioral and pathological results related to brain injury and used a random-effects model to calculate the standardized mean difference and confidence interval.</div></div><div><h3>Results</h3><div>Twenty-five articles met the inclusion criteria. Treatment with SC-EVs improved cerebral infarct size and tissue edema, as well as the recovery of cognition and motor function. The mechanism of action may be related to the inhibition of apoptosis, microglia activation, astrogliosis, and pro-inflammatory factor release, further promoting neuronal protection, remyelination, and angiogenesis. Study quality assessment found no studies to be at high risk, and there was significant heterogeneity among studies. Sensitivity analysis and subgroup analysis did not identify the source of heterogeneity.</div></div><div><h3>Conclusion</h3><div>SC-EVs might improve cognitive and motor functions, as well as brain microstructure, by exerting anti-apoptotic and anti-neuroinflammatory effects. This provides a theoretical basis for using cell-free therapies to prevent and treat PBI and supports the translation of SC-EVs from preclinical models to human applications.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111481"},"PeriodicalIF":3.7,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741270","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":"Neural network classification of Barnes maze search strategy utilization","authors":"Scott Ferguson,&nbsp;Coral Hahn-Townsend,&nbsp;Benoit Mouzon,&nbsp;Salina Yathiraj,&nbsp;Giovanni Brunetti,&nbsp;Nicole Saltiel,&nbsp;Cillian E. Lynch,&nbsp;Michael Mullan,&nbsp;Fiona Crawford","doi":"10.1016/j.brainresbull.2025.111483","DOIUrl":"10.1016/j.brainresbull.2025.111483","url":null,"abstract":"<div><div>The Barnes maze is a commonly used test of allocentric spatial reference memory, consisting of an elevated circular table with holes around the perimeter. Spatial cues surrounding the maze are intended to allow the animal on the maze to locate a target hole from which they can escape and return to their home cage during a period of acquisition trials. Following the acquisition period, the target box under the target hole is removed and a probe trial is performed to test spatial memory. One of the limitations of Barnes maze testing is that non-spatial strategies can be employed to locate the target hole, such as systematic serial searching hole to hole, which may mask the signal of spatial learning or memory deficits on gross outcome measures, such as the latency to find the target hole. Quantifying the search strategies used during Barnes maze testing can provide a more direct measurement of spatial memory impairments, and even allow for the detection of impairments to executive functioning and working memory that may impact the ability to utilize non-spatial systematic search strategies. We have developed a machine learning algorithm to automatically quantify search strategy utilization in an unbiased manner. Traumatic brain injury (TBI) is known to cause impairments in spatial learning and memory, and in our testing with a model of repetitive mild TBI we have found significant deficits in the utilization of both spatial and systematic non-spatial search strategies 3 months after TBI. Understanding the factors driving gross outcome measures on the Barnes maze may provide greater insight into the effectiveness of potential treatment strategies designed to mitigate the chronic effects of TBI and other neurodegenerative diseases.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111483"},"PeriodicalIF":3.7,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723026","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":"Neural dynamics impairments in amyotrophic lateral sclerosis patients and their associations with clinical characteristics: An observational cohort study","authors":"Wei Zheng ,&nbsp;Jing Luo ,&nbsp;Yong Yang ,&nbsp;Xia Guo ,&nbsp;Fei Song ,&nbsp;Feng Li ,&nbsp;Fei Xiao","doi":"10.1016/j.brainresbull.2025.111482","DOIUrl":"10.1016/j.brainresbull.2025.111482","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the central nervous system. It remains unclear whether pathological changes in ALS can lead to abnormalities in neural dynamics and how these abnormalities relate to key clinical characteristics of ALS.</div></div><div><h3>Methods</h3><div>Nonlinear neural dynamics analyses of electroencephalography (EEG) sensorimotor channels were conducted using recurrence quantification analysis (RQA), permutation Lempel-Ziv complexity (PLZC), shannon entropy (ShannonE) and permutation entropy (PermEn). Whole-brain spatiotemporal topological dynamics were assessed using microstate analysis.</div></div><div><h3>Results</h3><div>The study shows that the nonlinear neural dynamics across all frequency bands in the sensorimotor channels of ALS patients are impaired (reduction in Shannon Entropy of Diagonal Line Length Distribution [ENTR]). Frequency-specific nonlinear neural dynamics indicate increased nonlinear neural dynamics in high-frequency bands (with increases in PLZC in beta2 (20–25 Hz)). Nonlinear neural dynamics in low-frequency bands decreases (with decreases in ShannonE in theta (4–7 Hz)) and is negatively correlated with disease duration. ENTR across all frequency bands and ShannonE in the theta band of the sensorimotor channels are potential protective factors for ALS. Furthermore, sensorimotor channel analysis shows a close relationship with whole-brain spatiotemporal topological neural dynamics. Duration A is positively correlated with RR, DET and ENTR, while Occurrence B is negatively correlated with it.</div></div><div><h3>Conclusions</h3><div>The study demonstrates widespread abnormalities in the neural dynamics of ALS, which are closely related to clinical characteristics of ALS. There is also a close relationship between the neural dynamics of sensorimotor channels and whole-brain spatiotemporal topological dynamics in ALS patients.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111482"},"PeriodicalIF":3.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713410","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":"Sevoflurane reduces brain edema and improves blood-brain barrier by downregulating CaMKII to inhibit TMEM16A after cerebral ischemia injury both in vivo and in vitro","authors":"Jingbin Zhang ,&nbsp;Yuhe Tian ,&nbsp;Ruixue Wang ,&nbsp;Xinlei Qin ,&nbsp;Quntao Li ,&nbsp;Ketao Ma ,&nbsp;Junqiang Si ,&nbsp;Dong Zhao ,&nbsp;Yan Li ,&nbsp;Jiangwen Yin","doi":"10.1016/j.brainresbull.2025.111479","DOIUrl":"10.1016/j.brainresbull.2025.111479","url":null,"abstract":"<div><div>This study aimed to investigate whether sevoflurane could reduce brain edema and protect blood-brain barrier (BBB) after cerebral-ischemia injury in vivo and in vitro via calmodulin-dependent protein kinase II (CaMKII)/ transmembrane protein 16A (TMEM16A) pathway. Adult male Sprague-Dawley rats and the brain slices were respectively subjected to middle cerebral artery occlusion (MCAO) in vivo and oxygen-glucose deprivation (OGD) in vitro. Sevoflurane was intervened through a combination of pre-treatment and post-treatment in entire process. TMEM16A overexpression and knockdown was performed by adeno-associated virus. And using agonist and inhibitor affected CaMKII. Neurologic function, ultrastructure, brain water content and the integrity of blood-brain barrier were assessed. Protein levels were investigated by immunofluorescence and western blot. TMEM16A and AQP4 levels, brain water content, leakage of BBB increased in MCAO group. Claudin5 and ZO-1 levels decreased and neurological damage was aggravated after MCAO injury. Sevoflurane reduced brain edema, improved neurological function and protected BBB after MCAO by increasing Claudin5 and ZO-1 levels and decreasing TMEM16A and AQP4 levels. The effect of sevoflurane was weakened by overexpression of TMEM16A and enhanced by knockout of its expression. And when using the inhibitor KN-93, CaMKII level increased while TMEM16A level decreased, enhancing the neuroprotective effect of sevoflurane. Conversely, the effect of sevoflurane was weakened after using the agonist CALP1. Similarly, these manifestations were also observed after OGD injury. In brief, our findings suggest sevoflurane could reduce brain edema, and protect the BBB after cerebral ischemia-reperfusion injury which are related to the downregulation of CaMKII to inhibit TMEM16A.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111479"},"PeriodicalIF":3.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717563","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":"Impact of 5-ALA-induced PPIX accumulation on neural stem cell behavior","authors":"Elham Poonaki ,&nbsp;Sedra Badlah ,&nbsp;Ulf Dietrich Kahlert ,&nbsp;Sven G. Meuth ,&nbsp;Walter Stummer ,&nbsp;Ali Gorji","doi":"10.1016/j.brainresbull.2025.111480","DOIUrl":"10.1016/j.brainresbull.2025.111480","url":null,"abstract":"<div><div>5-aminolevulinic acid (5-ALA) is a widely recognized and effective tool for improving tumor resections during surgical interventions but may directly interact with cells in the tumor microenvironment. Nevertheless, there remains an ongoing debate regarding the impact of 5-ALA on neural stem cells (NSCs). This study aims to investigate the effects of 5-ALA on both NSCs and oligodendrocyte progenitor cells (OPCs). In this study, NSCs were isolated from the subventricular zones of rat brains and differentiated into OPCs. Both NSCs and OPCs were subsequently treated with 5-ALA, and their effects were evaluated through immunostaining and colony-formation assays. Our findings show that 5-ALA treatment induces PPIX accumulation in both NSCs and OPCs, with NSCs exhibiting higher levels presumably due to their greater proliferation rate. Furthermore, our results indicate that prolonged PPIX accumulation impairs NSC clonogenicity. These results underscore possible interactions of 5-ALA-induced PPIX with NSCs. 5-ALA shows promise as a potential marker for NSCs, but may also be of value for specifically targeting NSCs through activation of porphyrins using light or radiotherapy.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"229 ","pages":"Article 111480"},"PeriodicalIF":3.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717562","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":"Suhexiang pills inhibit ischemia stroke via targeting miR-24–3p to promote the activation of Keap1/Nrf2 signaling pathway","authors":"Zhaoshuo Li ,&nbsp;Mingcheng He ,&nbsp;KunPeng Wang ,&nbsp;Mi Zhang ,&nbsp;Wenxuan Lu ,&nbsp;Peng Zhang ,&nbsp;Li Zhang ,&nbsp;Zhigang Lu","doi":"10.1016/j.brainresbull.2025.111478","DOIUrl":"10.1016/j.brainresbull.2025.111478","url":null,"abstract":"<div><div>The incidence of ischemic stroke (IS) is increasing year by year in China and the world. Cerebral ischemia-reperfusion injury (CIRI) caused by blood flow restoration during treatment seriously affects the prognosis of the disease. Suhexiang pills (ShxP) is a traditional Chinese medicine prescription for the treatment of IS. Its composition is complicated and the mechanism by which it regulates IS remains unclear. In this study, a MicroRNA, miR-24–3p, was found to inhibit neuronal injury, inflammatory response and cell apoptosis induced by OGD/R stimulation through gain- and loss-function experiments. Consistently, miR-24–3p inhibits nerve damage, inflammatory activation, and apoptosis induced by t/MCAO surgery <em>in vivo</em>. Mechanically, miR-24–3p can inhibit Keap1 expression and activate the downstream Nrf2-HO-1 signaling pathway. More importantly, we found that ShxP administration can promote the expression of miR-24–3p in the OGD/R-stimulated neuron model. However, inhibition of miR-24–3p can reverse the protective effect of ShxP on OGD/R-stimulated neurons. On the one hand, this result proved the new function of miR-24–3p in regulating CIRI. On the other hand, it clarified the new mechanism of ShxP in inhibiting the progression of IS by promoting the expression of miR-24–3p. It provides a theoretical basis for the drug application of ShxP.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111478"},"PeriodicalIF":3.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717564","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}