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

{"title":"( +)-Catechin Alleviates CCI-Induced Neuropathic Pain by Modulating Microglia M1 and M2 Polarization via the TLR4/MyD88/NF-κB Signaling Pathway.","authors":"Bei Jing, Jia-Ji Zhao, Zhen-Ni Chen, Wai-Mei Si, Shi-Quan Chang, Ya-Chun Zheng, Zi-Feng Zhuang, Guo-Ping Zhao, Di Zhang","doi":"10.1007/s11481-025-10202-9","DOIUrl":"https://doi.org/10.1007/s11481-025-10202-9","url":null,"abstract":"<p><p>The aim of this research endeavor was to explore the therapeutic potential of ( +)-catechin in mitigating neuropathic pain. A total of thirty-two Sprague‒Dawley rats were randomly allocated into four groups: the sham group, the chronic constriction injury (CCI) group, the CCI + ibuprofen group, and the CCI + ( +)-catechin group. The results of the in vivo experiment show that ( +)-catechin has the potential to improve mechanical hyperalgesia induced by CCI and reduce the infiltration of inflammatory cells in the injured sciatic nerve. CCI induces the upregulation of nNOS, iNOS, IL-1β, and COX-2 within the rat sciatic nerve and leads to an elevation in the levels of IL-1β, PGE2, and TNF-α in the serum of rats, while simultaneously diminishing the secretion of IL-10. Moreover, immunofluorescence analysis reveals that CCI enhances the expression of CD32 (an M1 polarization marker) in the rat spinal cord, while diminishing the expression of CD206 (an M2 polarization marker). However, the administration of ( +)-catechin effectively counteracts these effects. Western blot analysis further demonstrates that ( +)-catechin significantly reduces the protein expression of IBA-1, IL-1β, MyD88, p-NF-κB, p-JNK, p-ERK, p-p38MAPK, COX-2, and TLR4 within the spinal cord. The findings of the BV2 cell experiment revealed the attenuating effects of ( +)-catechin on M1 polarization markers (such as IL-1β, TNF-α, iNOS, and CD32), while concurrently boosting the levels of M2 polarization markers (including CD206, IL-10, and Arg-1). Notably, administration of LPS significantly heightened the accumulation of IBA-1, IL-1β, MyD88, p-NF-κB, p-JNK, p-ERK, p-p38MAPK, TLR4, COX-2, and iNOS, while concurrently suppressing Arg-1 expression. However, the administration of ( +)-catechin effectively reversed these alterations. Overall, these findings suggest that ( +)-catechin alleviates neuropathic pain by modulating the M1 and M2 phenotypes of microglia through the TLR4/MyD88/NF-κB pathway.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"33"},"PeriodicalIF":6.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804998","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":"Pentoxifylline Prevents Neuroinflammation and Modifies PTEN/TrkB Signaling in an LPS-Induced Depression Model.","authors":"Tahir Ali, Yanhua Luo, Chengyou Zheng, Shafiq Ur Rahman, Iram Murtaza, Jinxing Feng, Shupeng Li","doi":"10.1007/s11481-025-10193-7","DOIUrl":"10.1007/s11481-025-10193-7","url":null,"abstract":"<p><p>Neuroinflammation affects patients with major depressive disorder and is linked to severe, treatment-resistant symptoms, making it a promising therapeutic target for improving depressive symptoms. This study highlighted the neuroprotective role of pentoxifylline (PTX) against lipopolysaccharide (LPS)-induced neuroinflammation and associated behavioral deficits. Mice were injected with LPS (1 mg/kg, i.p) to induce neuroinflammation and treated with PTX (10 mg/kg, i.p). Behavioral and biochemical analyses were performed to evaluate depressive-like behaviors and examine hippocampal protein expression associated with neuroinflammation and synaptic plasticity. LPS administration increased proinflammatory cytokine production (IL-1, IL6, and TNF-α), microglial activation (IBA-1/GFAP), and dysregulation of key synaptic proteins, including BDNF and TrkB, in the hippocampus of mice. Concomitantly, LPS reduced Phosphatase and tensin homolog (PTEN) phosphorylation, potentially contributing to increased neuroinflammation. PTX treatment effectively attenuated LPS-induced effects by suppressing inflammatory responses, restoring BDNF/TrkB signaling, and rescuing synaptic impairments. Mechanistically, PTX treatment increased PTEN phosphorylation and was reversed by the TrkB inhibitor K252a, suggesting that PTX upregulates TrkB/BDNF signaling, leading to increased PTEN phosphorylation and subsequent inhibition of PTEN activity. These findings highlight the potential of PTX as a therapeutic agent for neuroinflammatory conditions, possibly exerting its effects by modulating the PTEN/TrkB/BDNF signaling axis and suggest a novel mechanism of action involving the modulation of the PTEN/TrkB/BDNF signaling pathway.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"31"},"PeriodicalIF":6.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774773","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":"Dapagliflozin Ameliorate Type-2 Diabetes Associated Neuropathy via Regulation of IGF-1R Signaling.","authors":"Prabhsimran Kaur, Tashvinder Singh, Laxmipriya Jena, Tanya Gupta, Manjit Kaur Rana, Sandeep Singh, Randhir Singh, Puneet Kumar, Anjana Munshi","doi":"10.1007/s11481-025-10200-x","DOIUrl":"10.1007/s11481-025-10200-x","url":null,"abstract":"<p><p>Dapagliflozin, an approved SGLT2 inhibitor, has been shown to have extra-glycemic effects like cardio-reno protection. However, the neuroprotective effects of SGLT2 inhibitors against diabetic neuropathy (DN) have not been explored. The current study aimed to determine the neuroprotective potential of Dapagliflozin against STZ-NAD-induced DN in Wistar rats via IGF-1 signaling. DN was induced by STZ-NAD in male Wistar rats. After 60 days of induction, behavioural tests were conducted to access DN, and treatment with Dapagliflozin (0.75 mg/kg & 1.50 mg/kg) was initiated for 30 days. At the end of the study, the brain and sciatic nerve were isolated and expression analysis of IGF-1R signaling molecules was carried out using western blotting, qRTPCR, and immunohistochemistry. Structural changes in the brain and sciatic nerve were ascertained by histopathology. The results showed that treatment with Dapagliflozin improved behavioural parameters in STZ-NAD-induced DN rats. The decreased expression levels of IGF1R signaling pathway molecules and increased expression of p-AKT were found to increase and decrease in the brain and sciatic nerve, respectively after the treatment. Histological studies demonstrated the restoration of normal architecture of the brain and sciatic nerve after treatment with dapagliflozin. The altered expression of IGF-1R signaling molecules established the neuroprotective potential of dapagliflozin against DN.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"32"},"PeriodicalIF":6.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774758","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":"Revisiting Migraine Pathophysiology: from Neurons To Immune Cells Through Lens of Immune Regulatory Pathways.","authors":"Sugumar Subalakshmi, R Rushendran, Chitra Vellapandian","doi":"10.1007/s11481-025-10197-3","DOIUrl":"https://doi.org/10.1007/s11481-025-10197-3","url":null,"abstract":"<p><p>Migraine is a prevalent neurological disorder characterized by severe, recurrent headaches accompanied by symptoms, such as nausea, photophobia, and phonophobia, significantly affecting the quality of life of millions of people worldwide. Although the neurovascular pathway, involving blood vessel dilation and neurogenic inflammation, has been a cornerstone in understanding migraine pathophysiology. Emerging evidence suggests that immune dysregulation plays a pivotal role in the onset and progression of migraine. This review uniquely synthesizes recent advances linking immune regulatory pathways to migraine, an area that has not been widely explored in the literature. Specifically, we highlighted the involvement of CD4 + CD25 + regulatory T (Treg) cells, interleukins, and pro-inflammatory and anti-inflammatory cytokines, which have been implicated in pain signaling and immune imbalance in patients with migraine. Furthermore, genetic studies have provided compelling evidence by identifying associations between migraine susceptibility and immune-related polymorphisms, particularly in forkhead box P3 (FOXP3) and nuclear factor of activated T cells (NFAT). Moreover, the higher prevalence of migraine in individuals with comorbid autoimmune diseases further supports the hypothesis of a shared pathophysiological mechanism. Despite the growing recognition of immune involvement in migraine, its precise mechanisms remain unclear. By integrating key immune biomarkers and genetic insights, this review proposes a novel framework for understanding the immune-mediated pathways in migraine progression. Future research should focus on elucidating the specific immunological mechanisms underlying migraine, which could open new avenues for innovative, targeted therapeutic strategies.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"30"},"PeriodicalIF":6.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766109","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":"IL-17 A Exacerbated Neuroinflammatory and Neurodegenerative Biomarkers in Intranasal Amyloid-Beta Model of Alzheimer's Disease.","authors":"Avtar Singh Gautam, Shivam Kumar Pandey, Sneha Balki, Ekta Swarnmayee Panda, Rakesh Kumar Singh","doi":"10.1007/s11481-025-10192-8","DOIUrl":"https://doi.org/10.1007/s11481-025-10192-8","url":null,"abstract":"<p><p>Proinflammatory cytokines, especially interleukin-17 A (IL-17 A) have been found to be significantly associated with AD patients. IL-17 A amplifies neuroinflammation during AD pathology. This study highlighted the ability of IL-17 A to exacerbate amyloid-beta-induced pathology in animals. The AD pathology was induced with repeated intranasal administration of Aβ along with recombinant mouse IL-17 A (rmIL-17) at 1, 2 and 4 µg/kg for seven alternate days. Although, the combination of rmIL-17 and Aβ did not have severe effects on memory of the animals, but it drastically increased the IL-17 A mediated signaling, level of proinflammatory cytokines, oxidative stress and reduced antioxidants in the hippocampus and cortex regions of the animal brains. Interestingly, combining rmIL-17 with Aβ also triggered the expression of AD structural markers like pTau, amyloid-beta and BACE1 in the brain regions. Furthermore, rmIL-17 with Aβ exposure stimulated astrocytes and microglia leading to activation of proinflammatory signaling in the brain of the animals. These results showed the propensity of IL-17 A to promote severity of AD pathology and suggest IL-17 A as potent therapeutic target to control AD progression.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"29"},"PeriodicalIF":6.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756333","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":"Correction: Low-Dose Aspirin Upregulates Tyrosine Hydroxylase and Increases Dopamine Production in Dopaminergic Neurons: Implications for Parkinson's Disease.","authors":"Suresh B Rangasamy, Sridevi Dasarathi, Priyanka Pahan, Malabendu Jana, Kalipada Pahan","doi":"10.1007/s11481-025-10189-3","DOIUrl":"https://doi.org/10.1007/s11481-025-10189-3","url":null,"abstract":"","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"28"},"PeriodicalIF":6.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733115","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":"Modulating Multiple Molecular Trajectories by Nutraceuticals and/or Physical Activity in Attention-Deficit/Hyperactivity Disorder (ADHD)-Like Behaviors in Rat Pups.","authors":"Karema Abu-Elfotuh, Gellan Alaa Mohamed Kamel, Mazin A A Najm, Ahmed M E Hamdan, Mona T Koullah, Rasha K E Fahmy, Heba Abdelnaser Aboelsoud, Manar A Alghusn, Budor R Albalawi, Ahmed M Atwa, Khaled R Abdelhakim, Abdou M A Elsharkawy, Ehsan K Mohamed, Nada S Abdou, Reema Almotairi, Hoda A Salem, Ayah M H Gowifel","doi":"10.1007/s11481-025-10188-4","DOIUrl":"10.1007/s11481-025-10188-4","url":null,"abstract":"<p><p>Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition affecting cognitive and social functions all over childhood. Monosodium glutamate (MSG) is a common food additive associated with ADHD-like symptoms in children. Nutraceuticals, like sesamol (SE) and astaxanthin (AST), or physical activity (PHA) were reported to possess beneficial effects on human health. Meanwhile, still their neuroprotective effect against ADHD has been poorly investigated. This study aimed to investigate the impact of SE, AST and PHA either separately or combined on ADHD-like behaviors induced by MSG in rat pups. Eighty-four male Sprague Dawley rat pups were randomly allocated into seven groups; control, MSG, (PHA + MSG), (SE + MSG), (AST + MSG), (SE + AST + MSG), and (COMB [PHA + SE + AST] + MSG) and treated for eight weeks. MSG-induced ADHD-like behavior was evaluated, via assessing behavioral outcomes; neurotransmitters' levels; five pathway biomarkers, coupled with histopathological and immunohistochemical studies. Rats exposed to PHA or treated with SE or AST either separately or combined exhibited enhanced attention, locomotor, and cognitive abilities, compared to MSG-intoxicated group. All treatments remarkably improved MSG-induced abnormalities in neurotransmitters' levels; biochemical markers; along with histological findings, via modulating HMGB1/RAGE/JAK-2/STAT-3, PI3K/AKT/CREB/BDNF, AMPK/SIRT-1 and PERK/CHOP pathways. Nevertheless, the combination of PHA with nutraceuticals (SE and AST) elicited more favorable effects in all measured parameters and histological findings, compared to other treated groups. In conclusion, this study revealed the superiority of the combination of nutraceuticals with PHA, over other standalone treatments, in amelioration of MSG-induced ADHD-like behaviors in rat pups, via fine-tuning of HMGB1/RAGE, PI3K/AKT/CREB/BDNF, AMPK/SIRT-1 and PERK/CHOP pathways.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"27"},"PeriodicalIF":6.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660006","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":"Intranasal Delivery of Lithium Salt Suppresses Inflammatory Pyroptosis in the Brain and Ameliorates Memory Loss and Depression-like Behavior in 5XFAD Mice.","authors":"Piplu Bhuiyan, Wenjia Zhang, Ge Liang, Bailin Jiang, Robert Vera, Rebecca Chae, Kyulee Kim, Lauren St Louis, Ying Wang, Jia Liu, De-Maw Chuang, Huafeng Wei","doi":"10.1007/s11481-025-10185-7","DOIUrl":"10.1007/s11481-025-10185-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Alzheimer's disease (AD) is a devastating neurodegenerative disease (AD) and has no treatment that can cure or halt the disease progression. This study explored the therapeutic potential of lithium salt dissolved in Ryanodex formulation vehicle (RFV) and delivered to the brain by intranasal application. We first compared lithium concentrations in the brain and blood of wild-type mice following intranasal or oral administration of lithium chloride (LiCl) dissolved in either RFV or water. The beneficial and side effects of intranasal versus oral LiCl in RFV in these mice were assessed and potential mechanisms underlying the efficacy of anti-inflammation and anti-pyroptosis in the brains were also investigated in both wild-type and 5XFAD Alzheimer's Disease (AD) mice brains.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;For the study of brain versus blood lithium concentrations, wild-type (WT) B6SJLF1/J mice at 2 months of age were treated with intranasal or oral LiCl (3 mmol/kg) dissolved in RFV or in water. Brain and blood lithium concentrations were measured at various times after drugs administration. Brain/blood lithium concentration ratios were then determined. For studying therapeutic efficacy versus side effects and their underlying mechanisms, 5XFAD and WT B6SJLF1/J mice were treated with intranasal LiCl (3 mmol/kg) daily, Monday to Friday each week, in RFV beginning at 2 or 9 months of age with a 12-week treatment duration. Animal behaviors were assessed for depression (tail suspension), cognition (fear conditioning and Y maze), olfaction (buried food test), and motor functions (rotarod) at the age of 5 and 12 months. Blood and brain tissue were harvested from these mice at 13 months. Blood biomarkers for the functions of thyroid (thyroid stimulating hormone, TSH) and kidney (creatinine) were measured using ELISA. Changes in protein expression levels of the endoplasmic reticulum Ca&lt;sup&gt;2+&lt;/sup&gt; release channels type 1 InsP&lt;sub&gt;3&lt;/sub&gt; receptors (InsP&lt;sub&gt;3&lt;/sub&gt;R-1), malondialdehyde (MDA)-modified proteins and 4-hydroxy-2-nonenal (4-HNE), pyroptosis regulatory proteins (NLR family pyrin domain containing 3 (NLRP3), cleaved caspase-1, N-terminal of Gasdermin D (GSDMD)), cytotoxic (IL-1β, IL-18, IL-6, TNF-α) and cytoprotective (IL-10) cytokines and synapse proteins (PSD-95, synapsin-1) were determined using immunoblotting. Mouse body weights were monitored regularly.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared to oral LiCl in RFV nanoparticles, intranasal treatment of WT mice with LiCl in RFV markedly decreased blood concentrations at the time range of 30-120 min. The ratio of brain/blood lithium concentration after intranasal lithium chloride in RFV significantly increased, in comparison to those after oral administration lithium chloride in RFV or intranasal administration of lithium chloride in water. Intranasal lithium chloride in RFV inhibited both memory loss and depressive behavior in adult and aged 5XFAD mice. Addition","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"26"},"PeriodicalIF":6.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652434","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":"Correction: Reduction of Lewy Body Pathology by Oral Cinnamon.","authors":"Sumita Raha, Debashis Dutta, Avik Roy, Kalipada Pahan","doi":"10.1007/s11481-025-10187-5","DOIUrl":"https://doi.org/10.1007/s11481-025-10187-5","url":null,"abstract":"","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"25"},"PeriodicalIF":6.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618010","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":"Mitigating Remote Organ-Induced Brain Injury in Renal Ischemia-Reperfusion: The Role of Oleuropein in Inhibiting Oxidative Stress, Inflammation, Ferroptosis, and Apoptosis in Male Rats.","authors":"Mohammad Ghaffarinasab, Ayat Kaeidi, Jalal Hassanshahi","doi":"10.1007/s11481-025-10184-8","DOIUrl":"10.1007/s11481-025-10184-8","url":null,"abstract":"<p><p>Renal ischemia-reperfusion (RIR) induces brain damage as a distant organ. Oleuropein has antioxidant properties. This study aimed to explore oleuropein's protective effects against brain injury following RIR in rats. Thirty-six male Wistar rats were divided into six groups (n = 6) including sham, oleuropein (200 mg/kg), RIR, and RIR groups treated with oleuropein (50, 100, and 200 mg/kg). 48 h after injury, blood urea nitrogen (BUN) and creatinine levels were surveyed. The western blotting analysis was performed to assay the interleukin-1 beta (IL-1β), IL-10, tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), Bcl-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), cleaved caspase-3, glutathione peroxidase-4 (GPX4), nuclear factor erythroid-related factor-2 (NRF2), solute carrier family 7, member 11 (SLC7A11), and anti-acyl-CoA synthetase long-chain family 4 (ACSL4) proteins in kidney and/or brain tissues. Also, malondialdehyde (MDA) and total antioxidant capacity (TAC) levels, the activity of GPx, catalase, and superoxide dismutase (SOD) were evaluated. Kidney and brain tissues damage scores (KTDS and BTDS) were determined by H&E staining method. Prussian blue staining was conducted to identify iron accumulation. RIR significantly increased BUN, serum creatinine levels, KTDS, BTDS, iron deposition, MDA concentration, Bax, cleaved caspase-3, IL-1β, TNF-α, NF-κB p65, ACSL4 proteins expression levels, while decreasing TAC content, SOD, GPx, and catalase activity, Bcl-2, GPX4, SLC7A11 and NRF2 proteins expression in kidney and/or brain tissue of RIR group versus the sham (P < 0.05). Moreover, oleuropein attenuated these indicators in the RIR + oleuropein (200 mg/kg) group versus the RIR group (P < 0.05). Our study showed that RIR induced brain damage, and oleuropein exhibited protective effects against brain injury induced by RIR, through inhibiting oxidative stress, inflammation, ferroptosis, and apoptosis mechanisms.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":"20 1","pages":"24"},"PeriodicalIF":6.2,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582410","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}