Neuroreport最新文献

{"title":"Puerarin suppresses the oxidative stress and activates the cyclic AMP (cAMP)/cAMP response element binding protein/brain-derived neurotrophic factor signaling pathway in alcohol withdrawal-induced depressive disorder via regulating obesity-associated protein-mediated N6-methyladenosine demethylation.","authors":"Yazhong Li, Zhong Liu, Jianhua Ma, Aizhao Tian, Jia Wang, Yang Xu, Jie Yang, Xin Yan","doi":"10.1097/WNR.0000000000002179","DOIUrl":"10.1097/WNR.0000000000002179","url":null,"abstract":"<p><strong>Objective: </strong>Puerarin, a bioactive isoflavone glycoside predominantly extracted from the root of the kudzu plant ( Pueraria lobata ), is a traditional Chinese medicinal herb widely used for centuries. Alcohol withdrawal-induced depression (AWIDD), a serious psychiatric disorder, is prevalent in society. This study aimed to investigate the role of puerarin in oxidative stress and cyclic AMP (cAMP)/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in AWIDD, as well as the underlying mechanism.</p><p><strong>Methods: </strong>An alcohol withdrawal rat model was established. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-px) were measured using commercial kits. The cAMP level was detected by ELISA. CREB and phospho-CREB protein levels were analyzed by Western blot. BDNF level was assessed by reverse transcription-quantitative PCR. Dot blot was used to assess the total N6-methyladenosine (m 6 A) level. The interaction between obesity-associated protein (FTO) and prostaglandin-endoperoxide synthase 1 (PTGS1) was examined through RNA immunoprecipitation and dual-luciferase reporter assays.</p><p><strong>Results: </strong>Puerarin decreased oxidative stress and increased the cAMP, p-CREB, and BDNF levels. Besides, puerarin increased FTO-mediated m 6 A demethylation in alcohol withdrawal rats. FTO inhibition increased oxidative stress and decreased the activation of cAMP/CREB/BDNF signaling pathway. Mechanistically, FTO weakened the stability of PTGS1 mRNA via m 6 A demethylation. Overexpression of PTGS1 reversed the reduction in oxidative stress and the activation of the cAMP/CREB/BDNF signaling pathway induced by FTO overexpression.</p><p><strong>Conclusion: </strong>Puerarin suppressed oxidative stress and activated the cAMP/CREB/BDNF signaling pathway in AWIDD via regulating FTO-mediated m 6 A demethylation.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"589-598"},"PeriodicalIF":1.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of miR-204-5p promotes nerve regeneration and functional recovery after hypoxic-ischemic brain damage in neonatal rats via the Wnt2/Ephrin-A2/EphA7 pathway.","authors":"Mengzao He, Yejun Zhao, Jinping Jiang, Ling Fan, Weinong Mo, Qiang Yao, Yanwen Wang, Minzhi He, Fangfang Shen","doi":"10.1097/WNR.0000000000002184","DOIUrl":"10.1097/WNR.0000000000002184","url":null,"abstract":"<p><strong>Objective: </strong>Neonatal hypoxic-ischemic brain damage (HIBD) can cause short- and long-term neurological damage. MicroRNA (miR)-204-5p is closely associated with nerve injury caused by brain injury, but its mechanism in HIBD is not very clear.</p><p><strong>Methods: </strong>The neonatal rat's HIBD model was constructed by the modified Rice-Vannucci method, and the expression of miR-204-5p was detected. After overexpression or knockdown of miR-204-5p and application of Wnt2 activator HLY78, the histopathological changes and neuronal degeneration in the hippocampal CA1 region were observed with pathological staining. The neurological function was assessed with a diving platform test and elevated plus-maze test. Nerve regeneration-related protein and Wnt2/Ephrin-A2 (Eph receptor-interacting proteins)/EphA7 (erythropoi-etin-producing hepatomocellular receptor) signaling pathway protein levels were detected by immunohistochemistry and western blot, respectively.</p><p><strong>Results: </strong>miR-204-5p was highly expressed in HIBD. When miR-204-5p was knocked down, the morphology of nerve cells and Nissl bodies was notably improved, Fluoro-Jade C and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells number was significantly reduced. The levels of brain-derived neurotrophic factor and growth-associated protein 43 were significantly increased, and the behavioral indicators of the diving platform and elevated plus-maze test were significantly alleviated. The nerve injury was repaired, and the Wnt2/Ephrin-A2/EphA7 signaling pathway protein was notably elevated. The overexpressed miR-204-5p aggravated the nerve injury in HIBD rats. After the application of HLY78, the neuropathological damage of HIBD rats was further repaired, and the nerve regeneration and function were also significantly improved.</p><p><strong>Conclusion: </strong>Knockdown of miR-204-5p can improve HIBD in neonatal rats by activating the Wnt2/Ephrin-A2/EphA7 signaling pathway to encourage nerve regeneration and functional recovery.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"609-622"},"PeriodicalIF":1.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnolol improves postoperative cognitive dysfunction in aged mice by activating the nuclear factor erythroid 2-related factor 2/antioxidant response element pathway.","authors":"Jingwen Hao, Qi Wan, Yuan Liu, Chanjuan Chen","doi":"10.1097/WNR.0000000000002177","DOIUrl":"10.1097/WNR.0000000000002177","url":null,"abstract":"<p><strong>Background: </strong>The incidence of postoperative cognitive dysfunction (POCD) in elderly patients is high and related to an increased postoperative mortality rate. Magnolol has the potential to improve cognitive function, but its therapeutic effects and mechanisms of action on POCD remain unclear.</p><p><strong>Methods: </strong>An aged mouse model of POCD was constructed using sevoflurane anesthesia and abdominal exploratory surgery. Magnolol was administered via intragastric gavage at doses of 10 or 20 mg/kg daily, starting 1 week before surgery. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown mice were used to investigate the role of the Nrf2/antioxidant response element (ARE) pathway in the therapeutic effects of magnolol on POCD.</p><p><strong>Results: </strong>In POCD mice, magnolol treatment significantly reduced the escape latency, increased crossing numbers in the platform quadrant and target quadrant dwell time, and enhanced the novel object recognition index. Meanwhile, under the action of magnolol, the morphology of hippocampal neurons was protected, the rate of cell apoptosis was reduced, and the expression of antiapoptotic protein B-cell lymphoma 2 was upregulated. Magnolol also reduced the levels of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin-1β, and reactive oxygen species, while increasing the levels of superoxide dismutase, glutathione, and glutathione peroxidase. In addition, magnolol activated proteins related to the Nrf2/ARE pathway. Notably, silencing Nrf2 weakened the effect of magnolol on improving cognitive function in POCD mice.</p><p><strong>Conclusion: </strong>Magnolol may effectively improve POCD in aged mice by activating the Nrf2/ARE pathway.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"578-588"},"PeriodicalIF":1.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of alectinib on germinal matrix hemorrhage-induced neonatal brain injury.","authors":"Xuhui Yin, Yiheng Wang, Xiaoli Zhang, Xixiao Zhu, Bing-Qiao Zhao","doi":"10.1097/WNR.0000000000002180","DOIUrl":"10.1097/WNR.0000000000002180","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the role of alectinib in a neonatal mouse model of germinal matrix hemorrhage (GMH).</p><p><strong>Methods: </strong>We induced GMH in postpartum day 5 mouse pups by injecting collagenase into the germinal matrix. Alectinib was administered intraperitoneally after GMH induction. Western blot, immunofluorescence staining, and quantitative PCR were performed to explore the effects of alectinib on oxidative stress, microglial number, proinflammatory cytokines expression, blood-brain barrier (BBB) damage, and cortical neuron loss. Cresyl violet and Prussian blue staining were used to detect the ventricular size, cerebral cortical atrophy, and hemorrhage burden. Novel object recognition and rotarod tests were used to determine the neurological function.</p><p><strong>Results: </strong>We found that anaplastic lymphoma kinase (ALK) was upregulated in the perihematomal areas following GMH and was presented in endothelial cells. Treatment with alectinib resulted in a reduction in oxidative stress, as shown by decreasing generation of reactive oxygen species, lipid peroxidation, and oxidative DNA at 3 days after GMH. Alectinib also attenuated the number of microglia, levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α, loss of BBB integrity ZO-1 and claudin-5, and disruption of BBB. These effects of alectinib were accompanied by reduced hemorrhage burden, cortical neuron loss and cerebral cortical atrophy, and improved motor coordination, cognitive and memory impairments at 23 days after GMH.</p><p><strong>Conclusion: </strong>Our data revealed that alectinib reduced oxidative stress, microglia number, and BBB permeability, thereby alleviating secondary brain injury in GMH. Therapies that inhibit ALK signaling may confer neuroprotection against GHM.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"599-608"},"PeriodicalIF":1.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissociable neural connectivity patterns for decision and outcome phases in the stag hunt game: evidence from electroencephalography weighted phase lag index analysis.","authors":"Xianjia Wang, Wei Cui","doi":"10.1097/WNR.0000000000002176","DOIUrl":"10.1097/WNR.0000000000002176","url":null,"abstract":"<p><p>This study aimed to investigate phase-based functional connectivity during decision-making and outcome evaluation in the stag hunt game using electroencephalography (EEG). Thirty-five healthy participants completed a repeated stag hunt task while EEG was recorded. Functional connectivity was assessed using the weighted phase lag index. Paired-sample t tests were conducted to compare connectivity strength between (a) cooperative vs. defective choices during the decision phase (200-300 ms, theta band) and (b) gain vs. loss feedback during the outcome phase (200-500 ms, delta band). During the decision phase, theta-band connectivity was significantly higher for defect choices in frontocentral and parietal electrode pairs (e.g. FC2-C4, CP4-FC2). During the outcome phase, gain feedback elicited stronger delta-band connectivity across frontoparietal and fronto-occipital networks (e.g. AF8-O1/O2, CP2-Cz, and PO7-AF8). These findings reveal distinct oscillatory connectivity patterns associated with social decision-making and reward evaluation. Defection involves enhanced frontoparietal theta synchronization linked to cognitive control, whereas gain feedback engages broader delta networks related to reward processing. This study provides novel insights into the neural dynamics of cooperation and defection in social contexts.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"555-561"},"PeriodicalIF":1.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the MyD88-JNK pathway promotes pathogenetic Th17 differentiation by induction of activin-A secretion and enhances experimental autoimmune encephalomyelitis.","authors":"Xiaohan Jin, Nianchao Zhang","doi":"10.1097/WNR.0000000000002183","DOIUrl":"10.1097/WNR.0000000000002183","url":null,"abstract":"<p><strong>Objective: </strong>Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, T helper 17 (Th17) cells play a key role in its pathogenesis. T cells constitute an important subtype of cells in the immune system and play diverse roles in fighting infections, targeting tumors, and regulating autoimmune responses. Under different conditions, T cells can differentiate into various specialized types each with unique functions in the immune system. Among them, Th17 cells are known to exhibit both pathogenic and nonpathogenic functions. Previous studies have demonstrated that pathogenic Th17 cells play a pivotal role in the pathogenesis of human MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Recent data have shown that autocrine activin-A induces pathogenic Th17 cells, which promote neuroinflammation. However, the upstream regulatory mechanisms remain unclear.</p><p><strong>Methods: </strong>We found that both interleukin (IL)-1β and IL-23 induce activin-A production through the myeloid differentiation primary response protein 88 (MyD88)-transforming growth factor-β-activated kinase 1 (TAK1)-c-Jun N-terminal kinase (JNK) axis under inflammatory conditions. Inhibition of MyD88 function significantly suppressed activin-A expression, which markedly impaired IL-17 production from T cells and ameliorated the disease in the EAE model.</p><p><strong>Results: </strong>Activation of the MyD88-JNK pathway by IL-1β and IL-23 promotes activin-A production in pathogenic Th17 cells and exacerbates EAE.</p><p><strong>Conclusions: </strong>MyD88 signaling in T cells may be an attractive clinical target for anti-inflammatory therapies for diseases of the central nervous system.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"623-630"},"PeriodicalIF":1.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal functional lateralization and functional connectivity in thyroid-associated ophthalmopathy: mechanistic links to transcriptomic signatures and neurotransmitter systems.","authors":"Rui-Yang Hu, Xin Huang","doi":"10.1097/WNR.0000000000002178","DOIUrl":"10.1097/WNR.0000000000002178","url":null,"abstract":"<p><strong>Background: </strong>Thyroid-associated ophthalmopathy (TAO), characterized by eyelid retraction, proptosis, extraocular muscle hypertrophy, and pathological elevation of intraorbital pressure, represents a potentially devastating autoimmune disorder affecting both ocular structure and visual function. Emerging evidence demonstrates significant neurophysiological correlations in TAO pathogenesis, manifesting cerebral hemispheric specialization and cooperation; however, conventional methodologies failed to account for inherent anatomical asymmetries between cerebral hemispheres. Therefore, the present study used a new data analysis method to systematically interrogate hemispheric specialization and cooperation in TAO, while concurrently exploring its multi-omics correlations with transcriptomic signatures and neuromodulatory receptors/transporters.</p><p><strong>Methods: </strong>A total of 32 patients with TAO and demographically matched healthy controls underwent high-resolution resting-state functional MRI. Whole-brain connectome matrices profiling autonomy index-functional homotope (CFH) interactions were generated to quantitatively characterize lateralized functional decoupling and transhemispheric coordination deficits in TAO. Voxel-wise aberrations in autonomy index/CFH metrics underwent multimodal correlation mapping with whole-transcriptome expression profiles and neurotransmitter receptor/transporter density atlases.</p><p><strong>Results: </strong>Patients with TAO had higher abnormal autonomy index expression in the left inferior temporal gyrus; CFH values were reduced in the left cuneus, right cuneus, left precuneus, right precuneus, and left superior parietal. Enrichment analysis of genes associated with abnormal autonomy index and CFH values, respectively, revealed that these genes were mainly involved in synaptic development and regulation. Finally, in the density correlation analysis of abnormal CFH values with neurotransmitter receptors/transporters, significant correlations were found for 5-hydroxytryptamine (5-HT) 1A R, 5-HT 2A R, CB 1 R, GABA A R, M 1 R, and mGlu 5 R.</p><p><strong>Conclusion: </strong>This multimodal investigation yields novel neurobiological insights into hemispheric dysregulation patterns in TAO, while elucidating the pathophysiological continuum of this complex disorder.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"562-577"},"PeriodicalIF":1.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Directional sensitivity of the auriculomotor system to transient central and lateralized auditory stimuli.","authors":"Andreas Schroeer, Farah I Corona-Strauss, Ronny Hannemann, Daniel J Strauss","doi":"10.1097/WNR.0000000000002194","DOIUrl":"https://doi.org/10.1097/WNR.0000000000002194","url":null,"abstract":"<p><strong>Background: </strong>Electromyographic (EMG) activity of auricular muscles in humans has been shown to be sensitive to the direction of auditory stimuli. Specifically, transient auricular EMG responses are significantly influenced by the laterality (left or right) and anteriority (in or outside the visual field) of auditory stimuli. As these factors co-occurred in previous research, this study aimed to isolate their influence, specifically of anteriority.</p><p><strong>Methods: </strong>EMG signals of several auricular muscles were recorded from 11 participants. Transient auditory stimuli were presented from central (0° and 180°) and lateralized positions behind the participants (±150°).</p><p><strong>Results: </strong>As previously reported, ipsilateral responses were significantly larger than contralateral responses. Surprisingly, however, responses recorded when stimuli were presented from 180° were also significantly smaller than ipsilateral responses, and approximately as large as contralateral responses. Responses generated by stimuli originating from 0° were extremely small, or almost nonexistent.</p><p><strong>Conclusion: </strong>The implication of these results is that the main driving force of these responses is the lateralization of the auditory stimuli, while the anteriority appears to be only a secondary, minor contributor in the absence of lateralization. This behavior of the vestigial pinna-orienting system could be interpreted as an attempt to aid sound localization when visual information is not available, by, for example, changing the frequency filter properties of the pinna or by introducing interaural level differences by reorienting one pinna. Future studies investigating the auriculomotor system should be aware that presenting transient stimuli from central locations at 0° or 180° could generate only minor responses.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reticulon 4 reflects endoplasmic reticulum stress in arginine vasopressin neurons.","authors":"Yohei Kawaguchi, Yuichi Hodai, Satoshi Naito, Yuichi Kondo, Tetsuro Tsumura, Takashi Miyata, Tomoko Kobayashi, Mariko Sugiyama, Takeshi Onoue, Shintaro Iwama, Hidetaka Suga, Ryoichi Banno, Hiroshi Arima, Daisuke Hagiwara","doi":"10.1097/WNR.0000000000002174","DOIUrl":"10.1097/WNR.0000000000002174","url":null,"abstract":"<p><strong>Objectives: </strong>Arginine vasopressin (AVP) is synthesized in the magnocellular supraoptic nucleus and paraventricular nuclei of the hypothalamus, where AVP neurons function under a consistently high demand for AVP production. AVP neurons are subject to endoplasmic reticulum (ER) stress even under basal conditions, and this ER stress is further exacerbated when AVP production increases due to dehydration. Reticulon (RTN) is essential for ER formation and stabilization and plays a critical role in membrane morphogenesis within the ER. This study aimed to investigate the expression of RTN family members in hypothalamic AVP neurons.</p><p><strong>Methods: </strong>Fluorescence immunohistochemistry and in-situ hybridization were employed to examine the expression of RTN family members in hypothalamic AVP neurons of adult male mice. Water deprivation and treatment with a chemical chaperone 4-phenylbutyric acid were used to increase and decrease the ER stress of AVP neurons, respectively.</p><p><strong>Results: </strong>Among the RTN family members, only RTN4 was found to be expressed in hypothalamic AVP neurons. RTN4 was colocalized with ER organelle markers, including immunoglobulin heavy chain binding protein and calnexin. Furthermore, RTN4 expression increased during ER stress induced by water deprivation. On the other hand, increased RTN4 expression by water deprivation was attenuated by 4-phenylbutyric acid treatment.</p><p><strong>Conclusions: </strong>Our results suggest that RTN4 expression in AVP neurons is closely associated with ER stress caused by increased protein production in neuroendocrine cells.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"540-546"},"PeriodicalIF":1.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocytic mitochondria modulate poststroke splenic immune responses, promote interleukin 10 production, and mediate neuroprotection after intracerebral hemorrhage.","authors":"Ryosuke Tashiro, Yuki Kitamura, Jesus Bautista-Garrido, Guanghua Sun, Gab Seok Kim, Jaroslaw Aronowski, Joo Eun Jung","doi":"10.1097/WNR.0000000000002175","DOIUrl":"10.1097/WNR.0000000000002175","url":null,"abstract":"<p><strong>Background: </strong>We recently demonstrated that systemically transplanted astrocytic mitochondria enter the intracerebral hemorrhage (ICH)-affected brain, where they protect the neurons by mitigating oxidative damage via upregulation of the manganese superoxide dismutase (Mn-SOD), ultimately contributing to functional recovery after ICH in mice. Although our previous study clearly demonstrated the beneficial effects of mitochondria within the brain, the effect of transferred mitochondria on the peripheral system was not yet studied. Thus, here, we studied the impact of astrocytic mitochondria transfer on post-ICH recovery and modulation of systemic immune responses.</p><p><strong>Methods: </strong>We used the autologous blood injection model for the mouse ICH surgery. Mice subjected to ICH received astrocytic mitochondria intravenously at 1 h, 7, and 14 days post-ICH onset, and the splenic immune responses of these mice were analyzed at 21 days. An ICH-like injury was induced in vitro using primary cultured neurons treated with recombinant interleukin-10, and cell viability, reactive oxygen species levels, and gene expressions were analyzed.</p><p><strong>Results: </strong>We demonstrate that systemic transplantation of astrocytic mitochondria increases the population of splenic B cells, production of interleukin-10 by B cells, and plasma interleukin-10 levels in mice after ICH. Furthermore, in the ICH-like injury in vitro , exogenous interleukin-10 (to model spleen-mediated interleukin-10 increase) upregulated Mn-SOD expression in the cultured neurons and promoted neuronal survival and neuroplasticity-related gene expressions, suggesting interleukin-10 role in cytoprotection and repair/recovery under ICH-like condition.</p><p><strong>Conclusions: </strong>Thus, systemic transfer of astrocytic mitochondria modulates post-ICH peripheral immune responses, which may participate in functional recovery.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"547-554"},"PeriodicalIF":1.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}