Neurochemical Research最新文献

{"title":"CALB2 Overexpression Attenuates Neuropathic Pain by Inhibiting Oxidative Stress and Modulating Microglia M1/M2 Polarization Through Activation of the cAMP/CREB Pathway.","authors":"Junxiu Jin, Xiang Xu, Xiaoling Xu, Mei Yin, Yuhua Yin","doi":"10.1007/s11064-025-04576-8","DOIUrl":"https://doi.org/10.1007/s11064-025-04576-8","url":null,"abstract":"<p><p>Neuropathic pain (NP) is a chronic condition with high morbidity. Current treatments to manage this pain are largely ineffective due to a limited understanding of the underlying mechanisms. Based on the GSE2636 and GSE24982 datasets, NP-associated differentially expressed genes (DEGs) were screened by the bioinformatics approach. A rat L5 spinal nerve ligation (SNL) model and lipopolysaccharide (LPS)-induced BV2 cell model were adopted. Two key genes were identified, including calbindin-2 (CALB2) and sodium voltage-gated channel alpha subunit 1 (SCN1A), both of which were downregulated in the SNL rat model. Immunofluorescence staining demonstrated partial colocalization of CALB2 with Iba1-positive microglia. CALB2 overexpression promoted viability and inhibited apoptosis of LPS-induced BV2 cells. CALB2 overexpression also facilitated the shift of microglia from M1 to M2 phenotype, as evidenced by decreased levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) and elevated levels of IL-10 and arginase 1 (ARG1). Additionally, after CALB2 overexpression, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were lowered, while the levels of glutathione (GSH) and superoxide dismutase (SOD) were increased. In SNL rats, CALB2 overexpression enhanced the paw withdrawal threshold and paw withdrawal latency. Mechanistically, CALB2 overexpression inhibited NP development by activating the cyclic adenosine monophosphate/cAMP response element-binding protein (cAMP/CREB) signaling pathway. CALB2 overexpression inhibits oxidative stress and promotes microglia transition from M1 to M2 phenotype by activating the cAMP/CREB pathway, which in turn attenuates NP.</p>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 6","pages":"333"},"PeriodicalIF":3.8,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342515","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":"Advancing Cell Therapy to Enhance Passive Avoidance Memory: Integrative Approaches Combining Neural-Like Cells and Rosmarinic Acid Through Behavioral, Molecular, and Histological Analyses.","authors":"Elham Hoveizi, Golamreza Bijavi, Hoda Parsa","doi":"10.1007/s11064-025-04581-x","DOIUrl":"https://doi.org/10.1007/s11064-025-04581-x","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by progressive neurodegeneration, synaptic dysfunction, and cognitive decline. Regenerative strategies aim to replace lost neurons and modulate the inflammatory milieu to restore neural networks. This study examined the effects of neural-like cells (NLCs) derived from dental pulp mesenchymal stem cells (DPSCs) on a chitosan scaffold using rosmarinic acid (RA) in AD rats. In this study, DPSCs were extracted from teeth, characterized and differentiated, induced an AD model by destroying the Meynert nucleus, conducted passive avoidance tests, analyzed histology and immunohistochemistry, and measured inflammatory and oxidative stress markers. The extraction and differentiation of DPSCs were successful. Differentiated DPSCs into neural progenitors showed increased expression of Tuj-1, Map2, Nestin, and NF (RT-PCR, p < 0.001). Behavioral tests confirmed the AD model after seven days, and histology showed neuronal loss and gliosis following Meynert destruction. Histomorphology revealed improved brain tissue and significantly increased choline acetyltransferase (ChAT) expression in the treatment groups. Notable behavioral improvements were observed in the Y‑maze and shuttle box for treated rats compared with the AD group. Biochemical analyses showed a significant decrease in inflammatory markers IL‑1β, IL‑6, and TNF‑α, along with increases in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) in the RA-treated groups. The results provide reliable evidence that DPSCs, in combination with RA, exert a promising therapeutic effect and represent a meaningful advance toward the clinical application of combination therapies for patients with AD.</p>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 6","pages":"334"},"PeriodicalIF":3.8,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342507","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":"Refining our Understanding of Iron Overload Regulation in CIRI: Addressing Misinterpretations.","authors":"Kuan Yao, Xiaoyu Wang, Tao Jiang","doi":"10.1007/s11064-025-04583-9","DOIUrl":"https://doi.org/10.1007/s11064-025-04583-9","url":null,"abstract":"","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 6","pages":"332"},"PeriodicalIF":3.8,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342535","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":"Antiseizure Effects of Mirtazapine in a Rat Model of Status Epilepticus Via Cannabinoid Receptor Modulation.","authors":"Ali Vafaei, Mohammad Amin Manavi, Samaneh Toutounchian, Maedeh Mohaghegh, Razieh Mohammad Jafari, Mohammad Amin Kharaghani, Ahmad Reza Dehpour","doi":"10.1007/s11064-025-04584-8","DOIUrl":"https://doi.org/10.1007/s11064-025-04584-8","url":null,"abstract":"<p><p>Status epilepticus (SE) is a severe neurological condition with high morbidity and mortality rates. Despite the availability of treatments, many cases remain refractory to standard therapies. In this study we investigated the possible anticonvulsant effects of mirtazapine in SE-induced rats, and further examined the underlying mechanisms contributing to its observed neuroprotective properties. Male Wistar rats were subjected to SE and pre-treated with different doses of mirtazapine (3, 10, 30, 50 mg/kg). Seizure severity using Racine's scale and latency of first seizure were assessed. The involvement of cannabinoid receptors was examined using AM-630, a CB2 antagonist (0.5 mg/kg). Diazepam (1 mg/kg), a GABA_A positive allosteric modulator, was co-administered with mirtazapine to assess potential involvement of GABA receptors in mirtazapine's effects. The effects of K_ATP channel modulation were studied using glibenclamide (3 mg/kg), a K_ATP channel blocker. Additionally, CB1 receptor and indoleamine-2,3-dioxygenase (IDO) expression levels were measured using western blotting. Also, effects of mirtazapine were assessed when administered after SE induction, both alone (3 and 30 mg/kg) and in combination with diazepam (1 mg/kg). Pre-treatment with mirtazapine at doses of 30 and 50 mg/kg significantly reduced seizure severity and increased the latency to the first seizure, indicating a dose-dependent anticonvulsant effect. The anticonvulsant effects were mediated through the activation of CB1 and CB2 receptors, as evidenced by inhibition of these effects by sub-effective dose of AM-630 and upregulation of CB1 receptor expression following mirtazapine treatment. Co-administration of sub-effective doses of diazepam and mirtazapine significantly increased the latency to seizures but did not reduce the SE severity score. Additionally, sub-effective dose of glibenclamide inhibited only the mirtazapine's effects in increasing the latency to seizures but not its reducing of seizure severity. IDO expression remained unchanged, suggesting that the kynurenine pathway may not play a significant role in mirtazapine's anticonvulsant effects in SE. Of note, Mirtazapine either alone or in combination with sub-effective doses of diazepam, did not affect seizures when administrated after SE induction. This study shows that only pre-treatment with mirtazapine can effectively prevent SE primarily through the activation of CB1 and CB2 cannabinoid receptors. Further studies, including clinical trials, are needed to validate these findings.</p>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 6","pages":"331"},"PeriodicalIF":3.8,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342451","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":"Treadmill Exercise Alleviates Neuroinflammation, Demyelination, and Apoptosis Induced by Hyperactivation of Microglia in the Hippocampus of Senescent Mice by Regulating the SIRT1/PPARγ Pathway","authors":"Yang Liu,&nbsp;Yuhao Liu,&nbsp;Youhua Wang,&nbsp;Wen Guo","doi":"10.1007/s11064-025-04577-7","DOIUrl":"10.1007/s11064-025-04577-7","url":null,"abstract":"<div><p>Cognitive dysfunction is a major feature of brain aging. However, there is no effective treatment for brain aging. Aerobic exercise is a non-side-effective intervention that is effective in neurodegenerative diseases such as aging. The aim of this study was to explore the potential of treadmill exercise in preventing oxidative stress-induced brain aging and neurodegenerative diseases by investigating the effects of treadmill exercise and its mechanisms in D-galactose-induced mice. The results showed that D-galactose-induced C57BL/6 mice exhibited cognitive deficits, myelin deficits, and increased neuronal apoptosis. Additionally, we observed significantly elevated average optical density values of IBA-1, a microglia-specific marker, in the senescent group. These were effectively mitigated following the treadmill exercise. The study also found that treadmill exercise increased the expression of Silent Information Regulator 1 (SIRT1) and Peroxisome proliferator-activated receptor γ<b> (</b>PPARγ<b>)</b> proteins, while decreasing the expression of p-NFKB. Immunofluorescence double-labeling further validated that SIRT1 and PPARγ co-localized and that treadmill exercise contributed to increased SIRT1 and PPARγ overlapping fluorescence intensity. Treadmill exercise decreased the expression of IL-1β and iNOS, and decreased the number of TUNEL-positive cells and the expression of the apoptosis executor caspase3. The results suggest that aerobic exercise has the potential to ameliorate the cognitive deficits observed in D-galactose mice by modulating the SIRT1/PPARγ signaling pathway to impede microglia-induced neuroinflammation and reduce apoptosis. Treadmill exercise appears to have the potential to be an effective treatment for attenuating microglia inflammation-induced brain aging and neurodegenerative diseases.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306751","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":"Valproate-Induced Autism and Sexual Hormone Disturbances: A Literature Review and Hypotheses","authors":"Guillaume Nicolet,&nbsp;Nicola Marchi,&nbsp;Julie Perroy,&nbsp;Hugo Peyre,&nbsp;Amaria Baghdadli,&nbsp;Marie-Christine Picot","doi":"10.1007/s11064-025-04582-w","DOIUrl":"10.1007/s11064-025-04582-w","url":null,"abstract":"<div><p>Autism spectrum disorders (ASD) are neurodevelopmental disorders whose aetiology remains obscure. Multiple human and animal studies have shown that prenatal exposure to valproate increases the risk of ASD in children. Although the mechanisms implicated are still poorly understood, several hypotheses have been put forward; one being that the alteration of the prenatal hormonal milieu could be involved. Indeed, hormone disruption was observed in women with epilepsy or bipolar disorder treated with valproate with an increased risk of experiencing hyperandrogenism or an androgen-associated pathology such as polycystic ovary syndrome (PCOS) or diabetes. This could be explained by an inhibition of aromatase, the enzyme responsible for the aromatisation of androgens into oestrogens. Hormone disruption could impair neurodevelopment through the involvement of the orphan retinoic acid receptor alpha (RORA), a nuclear receptor whose expression is regulated by dihydrotestosterone (DHT) as well as estradiol, and whose transcriptional targets are implicated in ASD. Moreover, neuroestradiol is a key regulator of neurodevelopment and the effects of its disruption seem to overlap with the consequences of prenatal exposition to valproate. Finally, the onset of autism seems to be more frequent when pregnancies were affected by conditions hormonal disturbances such as obesity, diabetes, pre eclampsia or prematurity. This provides a better understanding of valproate-induced autism patterns and opens up new avenues of research to better understand the development of this disorder.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296577","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":"Regulation of Ischemic Long-Term Potentiation in GluN2B and FKBP51 Underlying Cathodal Direct Current Stimulation","authors":"Chi-Wei Lee,&nbsp;Chih-Wei Tang,&nbsp;Ching-Hsiang Chang,&nbsp;Chu-Ming Chia,&nbsp;Tsung-Han Hsieh,&nbsp;Hsiang Chi,&nbsp;Hui-Ching Lin","doi":"10.1007/s11064-025-04578-6","DOIUrl":"10.1007/s11064-025-04578-6","url":null,"abstract":"<div><p>Pathological synaptic plasticity, manifested as ischemic long-term potentiation, drives neuronal hyperexcitability following oxygen-glucose deprivation. While ischemic long-term potentiation (iLTP) is mediated by excessive GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) activity, the molecular mechanisms sustaining this aberrant plasticity remain poorly understood. FK506-binding protein 51 (FKBP51), a stress-related modulator of plasticity, has emerged as a potential regulator; however, its role in iLTP has not yet been explored. Cathodal direct current stimulation (cDCS), known to suppress pathological hyperexcitability, may offer therapeutic modulation of this process. In this study, we demonstrated that oxygen-glucose deprivation (OGD) induces iLTP alongside FKBP51 upregulation and GluN2B surface accumulation. Genetic deletion of FKBP51 or its pharmacological inhibition (SAFit2, 0.5 µM) normalized synaptic strength and GluN2B expression, establishing FKBP51’s critical role in maintaining iLTP. Notably, cDCS intervention replicated these protective effects, attenuating both iLTP and FKBP51 elevation. Our findings identify FKBP51 as a key mediator of ischemic synaptic dysfunction and suggest that cDCS may exert its therapeutic effects through FKBP51-dependent regulation of plasticity, thereby offering new targets for the treatment of ischemic brain injury.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia-Derived Exosomal miR-223-3p Targets the RhoB-NF-κB-CCL11 Axis in Astrocytes and Relieves Neuronal Damage in Subarachnoid Hemorrhage","authors":"Fanmeng Zeng,&nbsp;Zhirui Liao,&nbsp;Lei Li,&nbsp;Bo Yang,&nbsp;Jinshui Lin","doi":"10.1007/s11064-025-04566-w","DOIUrl":"10.1007/s11064-025-04566-w","url":null,"abstract":"<div><p>Neuroinflammation mediated by reactive microglia and astrocytes is the primary pathological process of early brain injury (EBI) after subarachnoid hemorrhage (SAH). This study aimed to investigate the role of microglia-derived exosomes in astrocytic activation and neuronal damage in SAH. An SAH mouse model was generated via endovascular perforation. Following the administration of miR-223-3p-enriched microglia-derived exosomes or a CCL11 antibody (anti-CCL11), the neurological functions of mice were evaluated. Nissl staining and TUNEL staining were carried out to assess neuronal apoptosis. The activation of microglia and astrocytes was examined by immunofluorescence. Hemin-treated primary cultured microglia and astrocytes were then cocultured with miR-223-3p-enriched exosomes or anti-CCL11. Furthermore, the conditioned medium of the cells was collected and added to HT22 cells. The viability, ROS level, and degree of oxidative stress in HT22 cells were determined. The mechanism of miR-223-3p to target RhoB was verified via a dual-luciferase reporter gene assay. Reduced miR-223-3p expression was detected in SAH mice, whereas CCL11 and inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-18) were elevated. Microglia-derived exosomal miR-223-3p or anti-CCL11 significantly mitigated neurological deficits and neuronal damage, and relieved microglial and astrocytic activation in the SAH model. In vitro experiments revealed that hemin induced significant activation of microglia and astrocytes. MiR-223-3p-enriched exosomes or anti-CCL11 attenuated hemin-induced microglial and astrocytic activation and attenuated HT22 cell damage through the inhibition of ROS and oxidative stress. Mechanistic studies revealed that miR-223-3p targeted RhoB and inhibited the RhoB/NF-κB/CCL11 axis in astrocytes. Microglia-derived exosomal miR-223-3p relieves EBI after SAH through the inhibition of astrocytic activation via the RhoB-NF-κB-CCL11 pathway.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285469","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":"d-Serine’s Journey Between Stars and Synapses","authors":"Sarah Mountadem,&nbsp;Stéphane Henri Richard Oliet,&nbsp;Aude Panatier","doi":"10.1007/s11064-025-04564-y","DOIUrl":"10.1007/s11064-025-04564-y","url":null,"abstract":"<div><p>Astrocytes play a pivotal role in regulating synaptic transmission, with <span>d</span>-serine emerging as a key gliotransmitter shaping NMDA receptor-dependent functions. This review is focusing on the multifaceted role of astrocytic <span>d</span>-serine from synaptic transmission to cognitive processes. While this review includes the work of other groups, it is mainly based on the findings obtained in our laboratory. Drawing from two decades of research spanning from the hypothalamus to the hippocampus, we here highlight how astrocyte-derived <span>d</span>-serine regulates NMDAR activity, long-term synaptic plasticity, and associated memory. Our findings have revealed the dynamic control exerted by astrocytic processes onto <span>d</span>-serine availability within the synaptic cleft, including the impact of the astrocytic morphological plasticity, the key role played by intracellular Ca²⁺ as well as the involvement of CB1 and EphB3 receptors. We also discuss how an impairment in astrocytic <span>d</span>-serine synthesis can affect the co-agonist availability and consequently impact cognitive functions in neurodegenerative disorders such as Alzheimer’s Disease. To conclude, this review highlights the role of astrocytic <span>d</span>-serine in astrocyte-neuron communication and higher-order brain functions.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12521327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraorbital Electroacupuncture Promotes Oculomotor Nerve Repair by Inducing M2 Macrophage Polarization via the JAK1/STAT6 Pathway","authors":"Yuan Li,&nbsp;Yi-fei Fan,&nbsp;Xiao-lu Jin,&nbsp;Bing-bing He,&nbsp;Yu-fei Liu,&nbsp;Tong-yan Liu,&nbsp;Ling-yun Zhou","doi":"10.1007/s11064-025-04517-5","DOIUrl":"10.1007/s11064-025-04517-5","url":null,"abstract":"<div><p>Oculomotor nerve injury impairs eye movement and pupil control. Intraorbital electroacupuncture (IEA) is a promising treatment, but its mechanisms remain unclear. This study investigates whether IEA promotes nerve recovery by inducing M2 macrophage polarization through the JAK1/STAT6 pathway. Sprague–Dawley (SD) rats with oculomotor nerve injury were divided into four groups: sham, control, IEA, and IEA + AS1517499 (JAK1/STAT6 inhibitor). Pupil diameter and abduction deviation were measured. Nerve structure was assessed with Luxol fast blue and Nissl staining. Western blotting analyzed JAK1/STAT6 pathway activation, and immunofluorescence quantified M1/M2 macrophages. The IEA group showed significant functional recovery in the oculomotor nerve, as evidenced by improvements in pupil diameter and abduction deviation compared to the control group. Histological analysis revealed better preservation of nerve structure in the IEA group, with reduced signs of damage. Western blot results demonstrated increased phosphorylation of STAT6 in the IEA group, indicating activation of the JAK1/STAT6 pathway. Immunofluorescence double staining revealed a higher ratio of M2 (CD206+, CD163+) macrophages relative to M1(CD86+ , iNOS+) macrophages in the IEA group. This effect was diminished in the IEA + AS1517499 group, suggesting that the therapeutic benefits of IEA are mediated through the JAK1/STAT6 pathway and M2 macrophage polarization. IEA promotes oculomotor nerve repair by inducing M2 macrophage polarization via the JAK1/STAT6 pathway, offering a potential therapeutic strategy for nerve injury.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285429","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}