{"title":"Therapeutic potential of calcitriol in cerebral ischemia/reperfusion injury: In vivo and in silico insights into TLR4 and FGFR2 pathways","authors":"Fahimeh Ramshini , Javad Amini Mahabadi , Reza Bayat , Sayyed Alireza Talaei , Zeinab Vahidinia , Hassan Hassani Bafrani","doi":"10.1016/j.ibneur.2025.06.018","DOIUrl":"10.1016/j.ibneur.2025.06.018","url":null,"abstract":"<div><h3>Background</h3><div>Cerebral ischemic injury remains a major cause of high mortality, with limited effective treatments available. Inflammatory responses play a critical role in the pathophysiology of cerebral ischemia/reperfusion (I/R) injury. Suppressing inflammation is a key strategy for mitigating cerebral I/R injury, making it a promising therapeutic target for stroke. Vitamin D supplementation has been revealed to exhibit anti-inflammatory and neuroprotective properties during I/R injury; however, the underlying protective mechanisms are not yet fully understood. This study aimed to investigate the effects of post-ischemic calcitriol treatment on ischemic stroke, focusing specifically on the TLR4/MyD88/NF-κB and FGFR2 signaling pathways</div></div><div><h3>Methods</h3><div>Male Wistar rats were divided into three main groups: sham, I/R+ Vehicle, and I/R+ Calcitriol. An experimental I/R model was created by occluding the middle cerebral artery (MCA) for 1 h, followed by a 72-h reperfusion period. Calcitriol (1 μg/kg) was administered intraperitoneally for three consecutive days post-stroke. Neurological deficit scores and infarct size were evaluated 72 h after MCAO. Gene expression levels of TLR4, MyD88, NF-κB, and FGFR2 in the brain cortex were measured using RT-PCR. Additionally, histopathological changes in the cortex were examined with Nissl staining. A molecular docking analysis was performed to investigate the interactions of calcitriol with TLR4 and FGFR2, providing insights into their binding affinities and potential functional implications.</div></div><div><h3>Results</h3><div>Our findings indicated that calcitriol treatment significantly enhanced neurological function (P < 0.05) and reduced infarct volume (P < 0.001) in cerebral I/R injury. Furthermore, calcitriol decreased the number of damaged neurons while markedly increasing the count of neurons with normal morphology (P < 0.001). Consistent with the results from molecular docking showing that calcitriol antagonizes TLR4 and FGFR2, RT-PCR analysis also revealed that calcitriol significantly suppressed the upregulation of TLR4 (P < 0.05), MyD88 (P < 0.01), NF-κB (P < 0.01), and FGFR2 (P < 0.001) mRNA expression levels.</div></div><div><h3>Conclusion</h3><div>The results demonstrate that calcitriol treatment offers significant neuroprotective benefits following cerebral I/R injury. These protective effects may be mediated, at least in part, by the inhibition of inflammation through the TLR4/MyD88/NF-κB and FGFR2 signaling pathways. This study enhances our understanding of the molecular mechanisms involved in calcitriol's neuroprotective actions.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 345-353"},"PeriodicalIF":2.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750471","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}
Jun-ya Okamura, Daisuke Fukano, Keisuke Murakami, Gang Wang
{"title":"View-invariant object representation in anterior and posterior inferotemporal cortex: A machine learning approach","authors":"Jun-ya Okamura, Daisuke Fukano, Keisuke Murakami, Gang Wang","doi":"10.1016/j.ibneur.2025.07.010","DOIUrl":"10.1016/j.ibneur.2025.07.010","url":null,"abstract":"<div><div>Inferotemporal (IT) cortex is the final visual area in the ventral stream where object information is processed. Previous electrophysiological studies showed viewing angle tolerance of 30–60° of single IT cells to the objects experienced in discrimination at each of several viewing angles, and to the objects experienced in learning association of different views. IT is divided into anterior (cytoarchitectonic area TE) and posterior (TEO) parts. It was reported that single cells in area TE showed the viewing angle tolerance while those in area TEO did not. In the present study population activities were compared between cell populations in area TE and those in area TEO using machine learning algorithm. An object set consisted of four similar objects created by deforming a prototype object, and four views each separated by 30°. A population vector was created by aligning responses of the cells to each object image. A classifier was trained by support vector machine (SVM) to create a hyperplane that separated one object from the other three objects at the same viewing angles, and then tested by response vectors to the object images at different viewing angles. In area TE, dynamics of the performance evaluated by d’ showed viewing angle tolerance of 30–90° to the objects with prior experience in learning association of different views. In area TEO, populations of the cells showed the viewing angle tolerance of 30°. Significant increase of the d’ values in area TE in the late time period for the objects with prior experience in learning association of different views may suggest view-invariance is more represented in late time period than early time period. These results suggest that viewpoint invariance is expressed more strongly in the TE region, and expressed in part in the population of the TEO cells.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 323-331"},"PeriodicalIF":2.9,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721711","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}
Di Wen , Qiusheng Li , Yuanyuan Li , Wenyu Yan , Yanyan Wang , Yakun Liu
{"title":"OPTN deficiency through CRISPR/Cas9 downregulates autophagy and mitophagy in a SOD1-G93A-expressing transgenic cell line","authors":"Di Wen , Qiusheng Li , Yuanyuan Li , Wenyu Yan , Yanyan Wang , Yakun Liu","doi":"10.1016/j.ibneur.2025.07.011","DOIUrl":"10.1016/j.ibneur.2025.07.011","url":null,"abstract":"<div><div>Amyotrophic lateral sclerosis (ALS) is characterized by the loss of upper and lower motor neurons (MNs) and is the most common adult paralysis neurodegenerative disease. Dysregulated autophagy, which has been reported in the pathogenesis of familial ALS, has been found in superoxide dismutase 1 (SOD1) transgenic mice and cell lines. Optineurin (OPTN) is a signal regulator that coordinates many crucial cellular processes, including autophagy, mitophagy and aggrephagy. Recent studies have shown that <em>OPTN</em> gene mutations are correlated with ALS, glaucoma and Paget’s disease of the bone. Indeed, defects in autophagosome–lysosome fusion have been reported in patients with ALS-associated <em>OPTN</em> mutations. However, the exact function of <em>OPTN</em> in the pathology of ALS remains unknown. To determine the function of OPTN, we generated <em>OPTN</em>-knockdown cell lines from SOD1-G93A-expressing NSC34 cells with the clustered regularly interspaced short palindromic repeats/associated system 9 (CRISPR/Cas9) approach. In our research, we observed that the loss of OPTN resulted in the impairment of autophagy and mitophagy pathways. Moreover, the mitochondrial transmembrane potential was depolarized by LV-sgRNA-OPTN. On the basis of observations of live cells, the production of reactive oxygen species (ROS) was increased, the autophagic flux decreased, and the autophagic flux merged with that of mitochondria according to confocal live-cell imaging. A decreased LC3-II and an increased p62 levels indicated that autophagy pathway activation was decreased. The protein levels of VDAC1 and TBK1 decreased after OPTN knockdown, suggesting that mitophagy was blocked. Our results suggest that OPTN plays a pivotal role in regulating autophagy and mitophagy.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 307-316"},"PeriodicalIF":2.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721709","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}
Mengzhi Liu , Yuqian Chen , Xinyan Fan , Jinmin Gu , Shihui Xing
{"title":"Beclin1-mediated vascular autophagy negatively regulates angiogenesis and secondary neural damage in the thalamus following cerebral cortical infarction","authors":"Mengzhi Liu , Yuqian Chen , Xinyan Fan , Jinmin Gu , Shihui Xing","doi":"10.1016/j.ibneur.2025.07.008","DOIUrl":"10.1016/j.ibneur.2025.07.008","url":null,"abstract":"<div><div>Focal cerebral infarction induces angiogenesis in the thalamus, which influences cognitive recovery. However, the mechanisms of angiogenesis in the thalamus remain unclear. This study was designed to investigate the potential role of Beclin1-mediated vascular autophagy in angiogenesis occurring in the thalamus after cerebral infarction. Cerebral infarction was induced by middle cerebral artery occlusion (MCAO). Cognitive function was evaluated using the Morris Water Maze. We assessed secondary neuronal damage, angiogenesis, Beclin1 expression and vascular autophagy in blood vessels of the ipsilateral thalamus. The functional effects of Beclin1 on vascular autophagy, angiogenesis and angiogenesis-related factors were determined using lentiviral-delivered siRNA. The results revealed significant angiogenesis in the ipsilateral thalamus at 7 days after MCAO, concurrent with elevated LC3-I to LC3-II conversion and increased Beclin1 expression in the ipsilateral thalamic vessels. Knockdown of Beclin1 markedly suppressed vascular autophagic activation and potentiated thalamic angiogenesis at the above time point. This enhanced angiogenesis correlated with significant reductions of neuronal loss and astrogliosis in the ipsilateral thalamus, alongside improved cognitive function. Furthermore, Beclin1 knockdown significantly increased the levels of angiopoietin-2 (ANG-2) and vascular endothelial growth factor (VEGF) in the ipsilateral thalamus after cerebral infarction. Collectively, these findings implicate that inhibition of Beclin1-mediated vascular autophagy enhances angiogenesis and mitigates secondary thalamic neuronal damage following cerebral infarction. This neuroprotective effect likely related to the restoration of ANG-2 and VEGF levels mediated by vascular autophagy in the thalamus.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 290-299"},"PeriodicalIF":2.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680317","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}
Minori Yamashita , Nito Nakahira , Kei Hashimoto , Hirono Kobayashi , Mari Nakashima , Hiroko Ikeshima-Kataoka , Yasunori Miyamoto
{"title":"Reactive astrocyte-derived neurotoxicity is mitigated by vitronectin in traumatic brain injury mouse model","authors":"Minori Yamashita , Nito Nakahira , Kei Hashimoto , Hirono Kobayashi , Mari Nakashima , Hiroko Ikeshima-Kataoka , Yasunori Miyamoto","doi":"10.1016/j.ibneur.2025.07.009","DOIUrl":"10.1016/j.ibneur.2025.07.009","url":null,"abstract":"<div><div>Vitronectin (VN) is an extracellular matrix protein that contributes to brain injury repair by regulating the fibrinolytic system. VN interacts with glial cells to regulate cytokine production. However, it is unclear how VN affects glial dynamics to promote repair of brain injury in a mouse model of traumatic brain injury (TBI). Here, we examined the effect of VN on astrocyte dynamics and neuronal cell death in mouse cerebral cortices after stab wounds. First, we verified that <em>Vn</em><sup><em>-/-</em></sup> cortices with stab wound surgery showed severe neuronal cell death and astrocyte activation around the lesion. In addition, the concentration of complement C3 was increased in <em>Vn</em><sup><em>-/-</em></sup> cortices after the stab wound, which was co-localized with astrocytes, suggesting that VN regulates astrocyte-derived C3 secretion and attenuates neurodegeneration after TBI. To further examine this, we collected secretions from VN-treated primary astrocytes and added them to primary cortical neurons, and found that secretions from VN-treated astrocytes have low neurotoxicity. Because the secretion from VN-treated astrocytes contained high levels of C3, we treated primary cortical neurons with the secretion from astrocytes and an inhibitor of the complement pathway, CD59, and analyzed neuronal cell death; results showed that inhibition of the complement pathway attenuates astrocyte secretion-induced neuronal apoptosis. Our results indicate that VN exerts a neuroprotective function through the suppression of C3 secretion from astrocytes. Therefore, VN plays a role in mitigating neurodegeneration after TBI by suppressing complement C3 secretion from reactive astrocytes.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 300-306"},"PeriodicalIF":2.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702577","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}
Yaqin Huang, Weiping Lei, Jiahong Shen, Jianliang Sun
{"title":"Tat-NR2B9c prevent cognitive dysfunction in mice modeling Alzheimer's Disease induced by Aβ1–42 via perturbing PSD-95 interactions with NR2B-subtype receptors","authors":"Yaqin Huang, Weiping Lei, Jiahong Shen, Jianliang Sun","doi":"10.1016/j.ibneur.2025.07.006","DOIUrl":"10.1016/j.ibneur.2025.07.006","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s Disease (AD) is one of common progressive and fatal neurodegenerative disorders,and its main clinical symptoms are progressive memory impairment and cognitive dysfunction. The Tat-NR2B9c, a peptide was known as postsynaptic density protein-95(PSD-95) inhibitors, has shown clinical efficacy as a neuroprotective effects in some diseases such as acute stroke and neuropathic pain.</div><div>The aim of the study is to clarify whether Tat-NR2B9c has the same neuroprotective effects in AD.</div></div><div><h3>Methods</h3><div>Studies were performed in mice modeling AD induced by Aβ<sub>1–42</sub>. Animals were treated with drugs after modeling AD for 14 days,and the spatial learning and memory ability were assessed after drug treatment. Then, mice were euthanized for biochemical tests.</div></div><div><h3>Results</h3><div>The levels of PSD-95 and NR2B decreased,and the levels of N-methyl-d-aspartate receptor–postsynaptic density protein-95 interaction increased in hippocampus in AD mice. Tat-NR2B9c can improve spatial learning and memory ability in AD mice by perturbing PSD-95 interactions with NR2B-subtype but not inhibiting PSD-95 levels.</div></div><div><h3>Conclusion</h3><div>Tat-NR2B9c can prevent cognitive dysfunction in mice modeling AD induced by Aβ1–42 via perturbing PSD-95 interactions with NR2B-subtype receptors.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 317-322"},"PeriodicalIF":2.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721710","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}
Zhu-Hong Fang , Yong Ni , Hong Xie , Hai-Long Zhang , Jia-Xuan Yang
{"title":"Pupillary ultrasonography vs Horner's syndrome to evaluate efficacy of stellate ganglion block in patients","authors":"Zhu-Hong Fang , Yong Ni , Hong Xie , Hai-Long Zhang , Jia-Xuan Yang","doi":"10.1016/j.ibneur.2025.07.007","DOIUrl":"10.1016/j.ibneur.2025.07.007","url":null,"abstract":"<div><div>Stellate ganglion block (SGB) is not only used for treating cervical thoracic, and upper limb pain-related diseases but also for treating sympathetic nervous system dysfunction-related diseases, and it is a widely used clinical treatment method. This study has demonstrated that utilizing ultrasound to measure pupillary diameter (PD) changes and significant inter-eye differences offers a more objective assessment of stellate ganglion block (SGB) efficacy compared to the traditional subjective evaluation based on Horner’s syndrome (HS). However, there is currently no objective standard to evaluate the efficacy of SGB. Pupillary ultrasonography can observe precise dynamic changes in the pupils, and is less affected by peripheral light, non-invasive, and convenient. We performed SGB under ultrasound guidance, and evaluated the effectiveness of SGB according to HS in 60 patients. All patients were scored using a visual analogue scale (VAS) before and 24 h after stellate ganglion block treatment. We compared the changes in pupil diameter (PD) and pupillary constriction ratio during pupil light reflex (PLR) in the blocked side and the opposite side. Then we calculated the inter-eye difference of PD before and after SGB, and the inter-eye difference of PD in the blocked side and the opposite side (BO-IED) at each time point. We found that the area under the curve (AUC) for evaluating the effectiveness of SGB was statistically significant at each time points for BO-IED and blocked side inter-eye difference. Additionally, the BO-IED at 15 min after SGB has the largest AUC, when the BO-IED is greater than 0.5 mm, which shows a sensitivity of 86.5 %, and a specificity of 100 %. Our findings suggested an association between pupil reduction and symptom reduction in patients, with the degree of pupil reduction serving as a reference for evaluating the effectiveness of SGB and the degree of symptom relief.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 264-271"},"PeriodicalIF":2.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655431","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}
Xiaoping Du, Jianzhong Lu, Zachary Yokell, Weihua Cheng, Don Nakmali, Richard D. Kopke, Matthew B. West
{"title":"Identification and quantification of GABAA R-α1-positive cells in the DCN of rats with behavioral evidence of noise-induced tinnitus","authors":"Xiaoping Du, Jianzhong Lu, Zachary Yokell, Weihua Cheng, Don Nakmali, Richard D. Kopke, Matthew B. West","doi":"10.1016/j.ibneur.2025.07.005","DOIUrl":"10.1016/j.ibneur.2025.07.005","url":null,"abstract":"<div><div>Tinnitus, the perception of a phantom sound, often occurs as a clinical sequela of auditory traumas. However, the underlying mechanisms of tinnitus are largely unknown. In our previous studies, we found more gamma-aminobutyric acid A receptor alpha 1 subunit (GABA<sub>A</sub>R-α1)-positive cells in the dorsal cochlear nucleus (DCN) after noise exposure, however, we were not able to identify the specific types of DCN cells that up-regulated GABA<sub>A</sub>R-α1 after the insult. In the current study, we used Nissl staining, Purkinje cell protein 4 (PCP4) and glutamic acid decarboxylase 67 (GAD67) immunolabeling to identify GABA<sub>A</sub>R-α1-positive cells in the DCN. Each type of GABA<sub>A</sub>R-α1-positive cells was quantified and statistically analyzed using immunostaining and Nissl staining according to their morphology, size and location in the DCN. GABA<sub>A</sub>R-α1-positive cartwheel cells, Golgi cells, as well as ML-stellate and vertical cells were confirmed by dual immunolabeling. In the DCN, the most common GABA<sub>A</sub>R-α1-positive cells were Golgi cells followed by vertical cells and cartwheel cells while very few other cells were GABA<sub>A</sub>R-α1-positive in all conditions. We found significantly more GABA<sub>A</sub>R-α1-positive Golgi cells in the DCN of noise-exposed rats without behavioral evidence of tinnitus compared to normal controls and noise-exposed rats with behavioral evidence of tinnitus. This heightened “context-dependent” inhibition may help to maintain a balanced neuronal network, preventing the potential for tinnitus-related hyperactivity in the auditory pathways.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 332-344"},"PeriodicalIF":2.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723060","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":"The nitrergic mechanism of geraniol in PTZ-induced seizures","authors":"Babak Shahhosseini , Hossein Tahmasebi Dehkordi , Hossein Amini-Khoei , Antoni Sureda , Mehrdad Shahrani , Zahra Lorigooini","doi":"10.1016/j.ibneur.2025.07.004","DOIUrl":"10.1016/j.ibneur.2025.07.004","url":null,"abstract":"<div><h3>Background</h3><div>This investigation aims to elucidate the role of NO in the anticonvulsant effects of Geraniol (GER) using a mouse model of pentylenetetrazole (PTZ)-induced seizures.</div></div><div><h3>Methods</h3><div>Mice were allocated into ten groups, including a control group receiving normal saline. The treatment groups received GER (10, 20, 30, and 40 mg/kg), L-NAME (10 mg/kg), L-arginine (L-arg) at 150 mg/kg, a sub-effective dose of GER (10 mg/kg) combined with L-NAME, and an effective dose of GER (40 mg/kg) plus L-arg, respectively. All drugs were administered <em>intraperitoneally</em> 30 min before seizure induction by <em>intravenous</em> infusion of PTZ. The last group served as the control for biochemical and molecular tests (no seizure induction). Subsequently, the seizure threshold was recorded. Nitrite levels in serum and the prefrontal cortex (PFC), as well as the gene expression of nNOS and iNOS in the PFC, were assessed.</div></div><div><h3>Results</h3><div>GER prolonged the seizure threshold and reduced serum and PFC nitrite levels. Also, it downregulated the gene expression of <em>nNOS</em> and <em>iNOS</em>. Simultaneous administration of L-arg with the effective GER dose (40 mg/kg) notably reversed the beneficial effects of GER. Conversely, when administered with a sub-effective dose of GER (10 mg/kg), L-NAME potentiated the effects of this dose of GER. The expression of the <em>nNOS</em> gene in the PFC significantly increased following the administration of 20 mg/kg GER and L-arg plus 40 mg/kg GER. Conversely, 40 mg/kg GER alone reduced <em>nNOS</em> gene expression in the PFC.</div></div><div><h3>Conclusion</h3><div>GER exhibits anticonvulsant properties by modulating the nitrergic system, increasing seizure latency, and reducing NO production. This suggests its potential as a therapeutic candidate for seizure management.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 257-263"},"PeriodicalIF":2.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632560","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":"Evaluation of the role of omega-3 fatty acids in nicotine-induced neurotoxicity in pregnant Wistar rats and their pups","authors":"Joseph Gbenga Omole , Quadri Kunle Alabi , Mayowa Grace Elemile , Ayodeji Aturamu , Modinat Adebukola Adefisayo , Gbenga Olatunde Omotosho , Samson Mokolade Ige , Orji Eunice Ibiye , Tokunbo Olorunfemi Samuel , Fisayo Nathaniel Ogunleye , Peace Kehinde Olamilosoye , Oladele Abiodun Ayoka","doi":"10.1016/j.ibneur.2025.07.003","DOIUrl":"10.1016/j.ibneur.2025.07.003","url":null,"abstract":"<div><div>This study investigated maternal and their pup neurobehaviour following nicotine exposure during gestational and postnatal periods and neuroprotective effect of Omega-3 fatty acids. Thus, the study used thirty pregnant female Wistar rats for this study. Groups I and II (nonpregnant and pregnant) were treated with 1 ml/kg/day of normal saline for 42 days; III was treated with 4 mg/kg/day of nicotine for 42 days; IV-VI were co-administered nicotine 4 mg/kg and 100, 300, 600 mg/kg/day of Omega-3 fatty acids respectively for 42 days. Results: The beam walk time of the mother rats in groups III and IV were significantly higher when compared with other groups. Similarly, the beam walks time of the pups of groups III and IV were significantly higher when compared with the pups of the mother rats in other groups. The brain dopamine and serotonin levels of mother rats in groups III, IV and V were significantly higher when compared with other groups. Also, the brain dopamine and serotonin levels of the pups in groups III and IV were significantly higher when compared with the pups in other groups. The reduced glutathione and catalase of mother and pup rats in groups III and IV were significantly lower when compared with other groups. Photomicrographs of cerebellum and hippocampus of the rats treated with nicotine showed scattered arrangement of pyramidal cells with vacuolated neurons. These alterations were significantly reversed with Omega-3 fatty acids following nicotine exposure. Conclusions. Omega-3 fatty acids at 300 and 600 mg/kg ameliorated nicotine-induced neurotoxicity in mother rats and their pups.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 272-289"},"PeriodicalIF":2.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680316","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}