Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology最新文献

{"title":"Exploring Dapagliflozin's Influence on Autophagic Flux in Mania-like Behaviour: Insights from the LKB1/AMPK/LC3 Pathway in a Mouse Model.","authors":"Nada K Saleh, Sama M Farrag, Mohamed F El-Yamany, Ahmed S Kamel","doi":"10.1007/s11481-025-10218-1","DOIUrl":"10.1007/s11481-025-10218-1","url":null,"abstract":"<p><p>Mania-like episodes are neuropsychiatric disturbances associated with bipolar disorder (BD). Autophagic flux disturbance evolved as one of the molecular mechanisms implicated in mania. Recently, Dapagliflozin (DAPA) has corrected autophagic signaling in several neurological disorders. Yet, no endeavours examined the autophagic impact of DAPA in mania-like behaviours. This study aimed to investigate the effect of DAPA on disrupted autophagic pathways in a mouse model of mania-like behaviour. Mania-like behaviour was induced through paradoxical sleep deprivation (PSD) using the multiple-platform method for a duration of 36 h. Mice were divided into three groups, with DAPA (1 mg/kg/day, orally) administered for one week. Behavioural assessments were conducted on the 7th day. DAPA mitigated anxiety-like behaviour in the open field test and improved motor coordination and muscle tone in the rotarod test. Mechanistically, DAPA activated hippocampal autophagy-related markers; liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) pathway, autophagy related gene 7 (ATG7), and microtubule-associated protein light chain 3II (LC3II). This was associated with reduced levels of the autophagosome receptor p62 protein, which subsequently enhanced GABA_A receptor-associated protein (GABARAP), facilitating the surface presentation of GABA_A receptors. Additionally, DAPA upregulated the GABA_B receptor R2 subunit through trophic factors such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Furthermore, DAPA mitigated elevated serum stress hormones and restored the balance between proinflammatory and anti-inflammatory cytokines in both cortical and hippocampal tissues. These findings highlight the role of autophagic flux modulation by DAPA and its therapeutic potential in mitigating mania-like behaviours.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"57"},"PeriodicalIF":6.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 Alters Inflammatory, Mitochondrial, and Protein Clearance Pathway Genes: Potential Implications for New-onset Parkinsonism in Patients.","authors":"Chukwunonso K Nwabufo","doi":"10.1007/s11481-025-10215-4","DOIUrl":"10.1007/s11481-025-10215-4","url":null,"abstract":"<p><p>Several preclinical and clinical studies have shown that SARS-CoV-2 infection is associated with new-onset Parkinson's disease (PD). The overall goal of this study is to uncover how the COVID-19 severity gradient impacts the conventional pathological pathway of PD to inform the identification of at-risk patients and the development of personalized treatment strategies. Transcriptomics analysis of 43 PD pathogenic genes was conducted on nasopharyngeal swabs from 50 COVID-19 patients with varying severity including 17 outpatients, 16 non-ICU, and 17 ICU patients, compared to 13 SARS-CoV-2 negative individuals. The study shows that COVID-19 severity gradient differentially dysregulates PD pathological genes. Dysfunctional lysosomal and mitochondrial processes in outpatients and non-ICU COVID-19 patients was identified as the convergent network of COVID-19-PD interactions. These dysfunctions were later abrogated by the upregulation of the ubiquitin-proteasome system and autophagy-lysosome system in ICU COVID-19 patients. A potential synergistic co-expression and clustering of protein clearance pathway genes with other pathological genes was observed in ICU patients, indicating a possible overlap in biological pathways. Dysregulation of the PD pathopharmacogene, SLC6A3 was observed in ICU patients, suggesting potential COVID-19-gene-drug interactions. Nasopharyngeal swabs express major PD pathological genes as well as clinically relevant drug processing genes, which could advance studies on PD, including diagnosis, pathogenesis, and the development of disease-modifying treatments. Outpatients and non-ICU COVID-19 patients may face a higher risk of developing new-onset PD, whereas ICU COVID-19 patients may be more susceptible to COVID-19-gene-drug interactions.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"58"},"PeriodicalIF":6.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonidine Ameliorates Neuroinflammation in the Rat Model of Tourette Syndrome.","authors":"Zhongling Ke, Yuxian Huang, Ang Wang, Yanhui Chen","doi":"10.1007/s11481-025-10214-5","DOIUrl":"https://doi.org/10.1007/s11481-025-10214-5","url":null,"abstract":"<p><p>Neuroinflammation plays a vital role in the etiology and pathogenesis of Tourette syndrome (TS). The postmortem report of TS patients clarified that IL-2 is elevated in the basal ganglia region, supporting neuroinflammation of TS. α₂ receptor agonist (clonidine) is one of the primary drugs for treating tic disorders; supported by clinical and animal experiments, α₂ receptor agonists have potential anti-inflammatory effects. This article aims to explore the impact of clonidine on neuroinflammation with TS and to reveal the possible mechanism of clonidine-mediated neuroinflammation with TS. Thirty P21 SD rats were randomly divided into a TS rat group (n = 20) and a normal control group (n = 10). After successful TS modelling, rats were randomly divided into the clonidine intervention group (n = 10) and the TS group (n = 10). The clonidine intervention group received clonidine 0.1 mg/kg by gavage daily for seven consecutive days. After behavioural evaluation on day 8, the brain was removed from the head. The striatum was separated from one side of the brain and subjected to ELISA to detect cytokines. The other side of the brain was subjected to immunohistochemical detection for microglial activation, and the integral optical density value was calculated using image software for comparison between the groups. Compared to the normal group, IL-2 cytokine levels in TS rats were significantly higher (P < 0.05). In the clonidine group, IL-2 levels (213.82 ± 121.48 pg/ml) were significantly lower than in the TS group (322.61 ± 79.27 pg/ml) (P < 0.05) but not significantly different from the normal control group (257.40 ± 95.80 pg/ml) (P > 0.05). Immunohistochemical analysis showed significant microglial activation in TS rats (IOD = 22.10 ± 6.67) compared to the normal group (IOD = 11.58 ± 4.36) (P < 0.05). Clonidine administration reduced microglial activation, with a significant difference between the TS + clonidine group (IOD = 15.97 ± 8.03) and TS rats (P < 0.05). Clonidine can suppress the neuroinflammatory response in Tourette syndrome, and its inhibitory effect on the neuroinflammatory response may be a potential beneficial effect of this treatment.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"56"},"PeriodicalIF":6.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limettin and PD98059 Mitigated Alzheimer's Disease Like Pathology Induced by Streptozotocin in Mouse Model: Role of p-ERK1/2/p-GSK-3β/p-CREB/BDNF Pathway.","authors":"Rofida M Hassan, Nesrine S Elsayed, Naglaa Assaf, Barbara Budzyńska, Krystyna Skalicka-Wożniak, Sherehan M Ibrahim","doi":"10.1007/s11481-025-10211-8","DOIUrl":"10.1007/s11481-025-10211-8","url":null,"abstract":"<p><p>Sporadic Alzheimer's disease (SAD) represents one of the major memory deficits that is characterized by tau hyperphosphorylation and amyloid beta (Aβ) deposition in the brain. Both are considered AD hallmarks which are mediated through neuroinflammation, oxidative stress, and cholinergic circuit interruption. This study aimed to show how limettin and PD98059 exert a neuroprotective effect against SAD and the possible role of the extracellular regulated kinase (p-ERK1/2) and glycogen synthase kinase-3 beta (p-GSK-3β) (Ser9)/cAMP-response element binding protein (p-CREB) (Ser133)/brain derived neurotrophic factor (BDNF) pathway. Control animals (Group I) received the vehicles, group II received PD98059 (10 mg/kg/i.p), while group III was administered limettin (15 mg/kg/i.p). Additionally, the other three groups received a single dose of streptozotocin (STZ; 3 mg/kg/ICV), where group IV served as the SAD group, while groups V and VI received PD98059 and limettin daily for 3 weeks, respectively. The SAD animals receiving PD98059 and limettin increased the number of arm entries, % alternations in Y-maze, with reduction in mean escape latency, increase in time spent in target quadrant and platform crossing in Morris Water Maze, compared to the SAD group. Additionally, PD98059 and limettin administration to the STZ group downregulated persistent activation of p-ERK1/2 which in turn increased p-GSK-3β (Ser9), leading to enhanced p-CREB (Ser133) and BDNF expressions, as well as reducing inflammatory markers viz., nuclear factor-kappa B and interleukin-6, leading to decreased Aβ deposition. Both treatments reduced immunohistochemical p-tau expression, brain edema, and increased intact neuron cells remarkably. Thus, based on these findings, PD98059 and limettin may have promising effects in protecting against SAD. Using blockers/inhibitory molecules are recommended to confirm effect through the corresponding pathway.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"55"},"PeriodicalIF":6.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COP1 Overexpression Attenuates Nociceptive Behaviors and Neuroinflammation in Cancer-Induced Bone Pain by Suppressing c/EBPβ.","authors":"Dan-Yang Li, Lin Liu, Shao-Jie Gao, Dai-Qiang Liu, Long-Qing Zhang, Jia-Yi Wu, Fan-He Song, Xin-Yi Dai, Ya-Qun Zhou, Wei Mei","doi":"10.1007/s11481-025-10217-2","DOIUrl":"https://doi.org/10.1007/s11481-025-10217-2","url":null,"abstract":"<p><p>Patients with advanced cancer often have bone metastases, causing bone destruction and cancer-induced bone pain (CIBP). The CCAAT/enhancer binding protein β (c/EBPβ) mediated the regulation of various pro-inflammatory molecules in microglia. To investigate the specific effect and regulatory mechanism of c/EBPβ in CIBP, a mice model of Lewis lung cancer (LLC) cells implantation was constructed. Our data demonstrated that the c/EBPβ was remarkably elevated in the spinal cord of CIBP mice. Specific knocking down c/EBPβ relieved the mechanical allodynia and thermal hyperalgesia of CIBP mice by suppressing the microglia activation and pro-inflammatory cytokines generation. Besides, overexpressing c/EBPβ could prompt severe pain behaviors with spinal neuroinflammation in naïve mice. Notably, the upstream regulator constitutive photomorphogenic 1 (COP1) was gradually reduced in the spinal cord of CIBP mice. Upregulating the expression of COP1 effectively alleviated the nociceptive behaviors of CIBP mice by inhibiting the accumulation of c/EBPβ and subsequent neuroinflammation. However, knocking down COP1 caused the rapid increase of c/EBPβ and exacerbation of spinal neuroinflammation, ultimately leading to behavioral damage in naïve mice. In conclusion, the absence of COP1 promoted the accumulation of c/EBPβ and neuroinflammatory molecules in the spinal cord of CIBP mice, which extends the future therapeutic approach for CIBP.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"54"},"PeriodicalIF":6.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effect of HMG-CoA Reductase Inhibitor Rosuvastatin on Doxorubicin-Induced Cognitive Impairment, Oxidative Stress and Neuroinflammation: Possible Role of CREB, ERK1/2, and BDNF.","authors":"Yesim Yeni, Betul Cicek, Ahmet Hacimuftuoglu, Mustafa Ozkaraca, Burak Batuhan Lacin","doi":"10.1007/s11481-025-10213-6","DOIUrl":"10.1007/s11481-025-10213-6","url":null,"abstract":"<p><p>During or after chemotherapy, cognitive impairments characterized by forgetfulness, difficulty concentrating, and depressive and anxiety-like symptoms are observed. There is limited research examining the effects of rosuvastatin (RVS), an HMG-CoA reductase inhibitor, in the context of neuroinflammation-related cognitive disruption. Here, we aimed to investigate the neuroprotective potential of RVS against doxorubicin (DOX)-induced cognitive impairments. Experimental groups were planned as control (normal saline, intraperitoneal), DOX (total cumulative dose 10 mg/kg, intraperitoneal), RVS (10 mg/kg, oral, 20 days), and RVS + DOX. Efficacy was monitored by applying a battery of behavioral assessments, as well as biochemical, genetic, histopathological, and immunohistochemical examinations. Results from Morris water maze (MWM), passive avoidance, locomotion activity, and elevated plus maze (EPM) tests showed that DOX administration caused behavioral disorders. Moreover, DOX increased the levels of inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α), while decreasing the levels of interleukin-10 (IL-10), glutathione (GSH), superoxide dismutase, catalase (SOD), endothelial nitric oxide (eNOS), and catalase (CAT). Co-treatment with RSV significantly attenuated DOX-induced behavioral changes and oxidative stress markers. In addition, similar to the immunohistochemical results, we determined that it increased the expression levels of extracellular signal-related kinases 1/2 (ERK1/2), cyclic adenosine monophosphate response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) and restored the histopathological structure of the brain. Therefore, these results indicated that RSV has a neuroprotective effect against DOX-induced cognitive impairment by reducing neurobehavioral impairments, exerting antioxidant and anti-inflammatory effects, and modulating brain growth factors.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"53"},"PeriodicalIF":6.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HucMSCs-Derived Extracellular Vesicles Deliver RPS27A Protein to Manipulate the MDM2-P53 Axis and Ameliorate Neurological Dysfunction in Parkinson's Disease.","authors":"Jinyu Xu, Hongbing Lei, Chunhui Yang, Yiqing Qiu, Xi Wu","doi":"10.1007/s11481-025-10209-2","DOIUrl":"https://doi.org/10.1007/s11481-025-10209-2","url":null,"abstract":"<p><p>Extracellular vesicles released from mesenchymal stem cells (MSCs-EV) have shown anti-inflammatory effects in Parkinson's disease (PD). This study was designed to assess the neuroprotective effects of human umbilical cord MSCs (hucMSCs) and the possible mechanisms involved. SH-SY5Y cells were induced with MPP⁺, and the impact of hucMSCs-EV on the damage to SH-SY5Y cells was examined. Mice were induced with PD-like symptoms by MPTP and the effects of hucMSCs-EV on neurological damage in mouse brain tissue were detected as well. HucMSCs-EV inhibited apoptosis and oxidative stress in MPP⁺-induced SH-SY5Y cells. HucMSCs-EV suppressed behavioral deficits and neuronal apoptosis in MPTP-induced mice, with an increased number of dopamine neurons in brain tissues and decreased p-alpha-syn expression in dopamine neurons. The expression of ribosomal protein S27A (RPS27A) in SH-SY5Y cells was elevated after co-culture of neurons and hucMSCs-EV, and RPS27A silencing abated the effect of hucMSCs-EV in vivo and in vitro. RPS27A bound to the MDM2 promoter, thus promoting P53 ubiquitination and degradation. MDM2 overexpression strengthened the therapeutic effect of hucMSCs-EV. We conclude that hucMSCs-EV promote the interaction between RPS27A and MDM2 by delivering RPS27A, which regulates the MDM2-P53 axis to promote degradation of P53 to ameliorate neurological damage in PD.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"52"},"PeriodicalIF":6.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible Interaction of Suramin with Thalamic P2X Receptors and NLRP3 Inflammasome Activation Alleviates Reserpine-Induced Fibromyalgia-Like Symptoms.","authors":"Maram M Mohamed, Hala F Zaki, Ahmed S Kamel","doi":"10.1007/s11481-025-10207-4","DOIUrl":"https://doi.org/10.1007/s11481-025-10207-4","url":null,"abstract":"<p><p>The high pain sensitivity in fibromyalgia (FM) is processed by the thalamus that presents as a key component in the pain pathway in FM patients. Noteworthy, Purinergic receptors, specifically P2X, are implicated in pain signaling and neuroinflammation via inflammasome signaling. However, there is no available data on the impact of pharmacological intervention on the P2X receptor in thalamic pain transmission in FM. To investigate this aspect, the clinically tested P2X inhibitor, Suramin (SURM), was utilized. FM was induced over three days using Reserpine (1 mg/kg/day, s.c.), followed by a single dose of SURM (100 mg/kg, i.p.). At the molecular level, SURM countered the overexpression of P2X7 and P2X4 receptors accompanied by reduced NLRP3 inflammasome complex and pyroptotic markers like gasdermin-D. This was associated with the suppression of the p38-MAPK and NF-κB pathways, along with a decrease in pro-inflammatory cytokines and tumor necrosis factor-α as observed by increased CD86 expression on M1 microglia phenotype, a neuroinflammatory marker. Concurrently, blocking the P2X receptor shifted microglia polarization towards the M2 phenotype, marked by elevated CD163 expression, as a neuroprotective mechanism. This was outlined by increased neurotrophic and anti-inflammatory IL-10 with normalization of disturbed neurotransmitters. Behaviorally, SURM ameliorated the heightened pain processing, as observed in mechanical and thermal pain tests. Furthermore, it lowered Reserpine-induced motor impairment in the rotarod and open-field tests. This improvement in the somatosensory experience was reflected in alleviating depressive-like behavior in the forced swimming test. These findings highlight the therapeutic potential of blocking thalamic P2X receptors in alleviating fibromyalgia symptoms.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"51"},"PeriodicalIF":6.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lycopene Supplemented Mediterranean Diet Ameliorates Experimental Autoimmune Encephalomyelitis (EAE) in Mice and Changes Intestinal Microbiome.","authors":"Tutku Atuk Kahraman, Müge Yılmaz, Kübra Aslan, Halit Canatan, Ayca Kara, Ozkan Ufuk Nalbantoglu, Aycan Gundogdu, Ahmet Eken","doi":"10.1007/s11481-025-10212-7","DOIUrl":"https://doi.org/10.1007/s11481-025-10212-7","url":null,"abstract":"<p><p>This study aimed to determine the effects of the Mediterranean diet (MD) and lycopene on the development of EAE and on inflammatory markers. In the 43-day study, 72 female C57BL/6 mice were randomly divided into eight groups according to whether they were EAE or naive (control) mice, fed a Western diet or a MD, and whether they received lycopene. During the study, mice were fed ad libitum, and lycopene groups were given 10 mg/kg/day lycopene per mouse every other day for 28 days in oral gavage. The mice were scored for EAE, sacrificed and their spleen, lymph nodes, and spinal cords were removed. We observed slightly delayed EAE onset in the MD-Lyc group compared to the others, and the EAE clinical scores were also lower than in the other groups. T-cell counts in the spleen and lymph nodes of the MD-Lyc group were significantly lower than in other groups. The production of IFN-γ and IL-22 was higher than in the other groups. IL-17 A cytokine produced in the spleen was lower in the MD-Lyc group than in the other groups. In addition, the highest myelination score was seen in the MD-Lyc group. MD-Lyc group also had a unique microbiome profile compared with the remaining groups. In summary, MD and lycopene administration positively impacted EAE scores and myelination. However, more comprehensive studies at the in vitro and in vivo levels are needed to reveal the effect of this intervention on cell numbers in the CNS.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"50"},"PeriodicalIF":6.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Anticonvulsant Effects of Pomalidomide by Targeting Oxidative Stress and Nrf2-Ho1 Signaling Pathway in Male Wistar Rats: A New Insight in Seizure Control.","authors":"Elnaz Khorasanian, Hassan Rajabi-Maham, Vahid Azizi, Abdolkarim Hosseini","doi":"10.1007/s11481-025-10205-6","DOIUrl":"https://doi.org/10.1007/s11481-025-10205-6","url":null,"abstract":"<p><p>Current medications for seizure symptoms can reduce seizure severity but do not stop or slow their progression. These drugs often have unpleasant side effects and may not work for all patients. The search for new therapeutic targets for seizure progression can be expedited through drug repurposing, which leverages existing approved medications, ultimately reducing clinical trial costs. This study investigates the neuroprotective properties of pomalidomide, an immunomodulatory drug, in a male rat model of pentylenetetrazol-induced seizures. Pomalidomide pretreatment significantly decreased the frequency and severity of seizures and delayed their onset. It elevated glutathione peroxidase (GPX) and superoxide dismutase (SOD) levels while lowering malondialdehyde (MDA), showcasing its antioxidant effects. Furthermore, it activated the Nrf2/HO-1 signaling pathway by increasing gene expression in the hippocampus, providing neuroprotection in the CA1 and CA3 regions. These findings suggest that pomalidomide may enhance the antioxidant defense system, support the Nrf2/HO-1 pathway, and protect the hippocampus, indicating its potential for treating patients with seizures, particularly intractable ones.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"49"},"PeriodicalIF":6.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}