IBRO Neuroscience Reports最新文献

{"title":"Ginkgolide B as a biopsychosocial treatment salvages repeated restraint stress-induced amygdalar anomalies in mice","authors":"Olusegun G. Adebayo ,&nbsp;Benneth Ben-Azu ,&nbsp;Wadioni Aduema ,&nbsp;Oyetola T. Oyebanjo ,&nbsp;Emmanuel U. Modo ,&nbsp;Iheagwam Pauline Ndidiamaka ,&nbsp;Spiff E. Eleazer ,&nbsp;Joseph Igbo Enya ,&nbsp;Abayomi M. Ajayi","doi":"10.1016/j.ibneur.2024.12.010","DOIUrl":"10.1016/j.ibneur.2024.12.010","url":null,"abstract":"<div><div>From preclinical and clinical findings, it has been shown that the amygdala is a critical mediator of stress and primary target for stress effects in the brain. We investigated the neuroprotective effect of Ginkgolide B (GB) in repeated restraint stress-induced behavioral deficit and amygdalar inflammation in mice. Mice were orally pre-treated with GB 20 mg/kg 1 h prior to 4 h restraint stress for 21 consecutive days. Behavioural deficit and serum and amygdalar biochemical changes were estimated using spectrophotometric and ELISA techniques. The results showed that GB pre-treatment inhibited spatial memory deficit, renounces neuropsychiatric phenotypes and metabolic redox activity by augmenting the endogenous antioxidant system via Nrf2 levels in the mice. The HPA axis activity impaired by the restraint stress induction was abated with marked reduction of corticosterone, hypertrophy of the adrenal gland and blood glucose level. Meanwhile, our data further reveals that GB pre-treatment inhibited the release of neuroinflammatory mediators (MPO, TNF-α, IL-6, MAPK, COX-2) and elevated CREB production via activation of BDNF protein. Further, the acetylcholinesterase activity was inhibited while the level of glutamate release remains unchanged in the amygdala of the restraint mice. The GB treatment also up-regulate the release of BCL-2 proteins. This study suggests that GB could be considered as a therapeutic agent in the management of memory impairment, neuropsychiatric phenotypes and neuropathological alterations.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 66-77"},"PeriodicalIF":2.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023097","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":"Postoperative analgesia with morphine promoting microglial activation and neuroinflammation induced by surgery aggravates perioperative neurocognitive dysfunction in aged mice","authors":"Xiuzhi Shao ,&nbsp;Liping Xie ,&nbsp;Jingwen Zhai ,&nbsp;Mingyue Ge","doi":"10.1016/j.ibneur.2024.12.008","DOIUrl":"10.1016/j.ibneur.2024.12.008","url":null,"abstract":"<div><h3>Introduction</h3><div>Perioperative neurocognitive dysfunction (PND) is a significant challenge for patients who need surgery worldwide. Morphine can trigger an intense inflammatory reaction in the central nervous system (CNS) at the same time as analgesia, thus adverse effects aggravating PND. Microglia polarization is closely involved in the regulation of neuroinflammation and the TLR4/MyD88/NF-κB signaling pathway. However, the mechanisms of morphine analgesia aggravating PND impairment remain unclear.</div></div><div><h3>Methods</h3><div>Tibial fracture surgery was performed in 18 months old male C57BL/6 J mice to mimic human orthopedic surgery and postoperative analgesia with morphine hypodermic or ropivacaine. Levels of inflammatory factors in the hippocampus, activation, and phenotype of microglia, an essential protein of TLR4/MyD88/NF-κB signal pathway, synaptic plasticity, and hippocampal-dependent memory function were evaluated after surgery and postoperative analgesia.</div></div><div><h3>Results</h3><div>Morphine postoperative analgesia increased the expression of pro-inflammatory cytokines IL-1 β, IL-6, and TNF-α, decreased the level of anti-inflammatory IL-10, aggravated the activation of microglia and the destruction of synaptic plasticity in the hippocampus, resulting in hippocampal neuron loss, a significant decrease in the number of synapses and cognitive impairment in aged mice. In addition, the aggravation of neuroinflammatory response and the activation of microglia may be mediated by TLR4/MyD88/NF- κ B signal pathway.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate that morphine postoperative analgesia may aggravate microglia activation and neuroinflammation in the hippocampus by regulating the TLR4/MyD88/NF- κ B signal pathway and inhibiting the synaptic plasticity hippocampal neurons. It aggravated the acute cognitive decline and cognitive impairment after tibial fracture in elderly mice.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 39-49"},"PeriodicalIF":2.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004766","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":"The relationship between fractional amplitude of low-frequency fluctuations (fALFF) and the severity of neglect in patients with unilateral spatial neglect (USN) after stroke: A functional near-infrared spectroscopy study","authors":"Shanshan Shi ,&nbsp;Jiaxing Meng ,&nbsp;Xiaohua Wu ,&nbsp;Jie Wang ,&nbsp;Hujun Wang ,&nbsp;Pengfei Li ,&nbsp;Shuyan Qie","doi":"10.1016/j.ibneur.2024.12.005","DOIUrl":"10.1016/j.ibneur.2024.12.005","url":null,"abstract":"<div><h3>Objective</h3><div>Unilateral spatial neglect (USN) following right hemisphere stroke is more pronounced, severe, and persistent than in the left hemisphere. However, the pathophysiological mechanisms underlying USN remain largely unknown. This study aims to investigate the relationship between the fractional amplitude of low-frequency fluctuations (fALFF) in the right hemisphere of patients with post-stroke USN and the severity of neglect using resting-state functional near-infrared spectroscopy (fNIRS) technology. This could provide new theoretical insights into the subtle changes in the pathophysiology of spontaneous neural activity in brain regions of patients with USN.</div></div><div><h3>Methods</h3><div>Seventeen patients with post-stroke USN (USN group) and twenty-four control subjects (control group) were selected. A 22-channel fNIRS system was used to test the hemodynamic signals of the right hemisphere at rest for all subjects. Data preprocessing and analysis were performed using the NIRS-KIT toolbox. Patients in the USN group were assessed using the Behavioral Inattention Test-Conventional (BIT-C) and the Catherine Bergego Scale (CBS). Differences in fALFF values across channels between the two groups were compared, and the fALFF values from channels showing significant differences in the USN group were correlated with scores on scales evaluating the severity of USN.</div></div><div><h3>Results</h3><div>(1) Significant differences in fALFF values were observed between the USN and control groups in specific channels, with channels CH6 and CH11 showing significantly lower fALFF values in the USN group compared to the control group (p &lt; 0.05), while channels CH12, CH16, and CH21 exhibited significantly higher fALFF values in the USN group (p &lt; 0.05). (2) In patients with USN, fALFF values in CH12 were significantly negatively correlated with BIT-C scores (r = -0.4966, p = 0.0443), and fALFF values in CH21 were also significantly negatively correlated with BIT-C scores (r = -0.5270, p = 0.0318). (3) Only the fALFF values in CH21 were significantly positively correlated with CBS scores in patients with USN (r = 0.5512, p = 0.0236).</div></div><div><h3>Conclusions</h3><div>The severity of symptoms of neglect towards the left side in patients with USN may be related to compensatory neural functional activity in the right dorsolateral prefrontal cortex area.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 31-38"},"PeriodicalIF":2.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983376","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":"An experimental EEG study of brain activities underlying the Autonomous Sensory Meridian Response","authors":"Ali Mohammadi ,&nbsp;Sahar Seifzadeh ,&nbsp;Fatemeh Torkamani ,&nbsp;Sina Salehi","doi":"10.1016/j.ibneur.2024.12.001","DOIUrl":"10.1016/j.ibneur.2024.12.001","url":null,"abstract":"<div><div>Autonomous Sensory Meridian Response (ASMR) is an audio-visual phenomenon that has recently become popular. Many people have reported experiencing a tingling-like sensation through their body while watching audio/video clips known as ASMR clips. People capable of having such experiences have also reported improved overall well-being and feeling relaxed. However, the neural activity underlying this phenomenon is not yet well-studied. The present study aims to investigate this issue using electroencephalography (EEG) employing an exploratory approach. We recorded resting-state EEGs from twelve participants before and after watching an ASMR clip and a control video clip. We divided the participants into two groups capable of experiencing ASMR tingling (ASMR group) and not capable of experiencing ASMR tingling (Non-ASMR group), by performing “Jenks Natural Breaks” clustering method on the results of a self-report questionnaire. We calculated the spectral power of EEG recording and compared the resulting values between the groups and sessions. We demonstrated a decline in the power of EEG activities in the delta frequency band in all regions of the brain and an increase in alpha activity in the occipital area of the brain and increases in beta oscillations was noted over the left fronto-temporal region of the brain among ASMR group. We did not observe similar results among the Non-ASMRs participants or among ASMRs in the control group.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 6-15"},"PeriodicalIF":2.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11722596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970669","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":"Effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesity","authors":"Julien Clain ,&nbsp;David Couret ,&nbsp;Matthieu Bringart ,&nbsp;Olivier Meilhac ,&nbsp;Christian Lefebvre d’Hellencourt ,&nbsp;Nicolas Diotel","doi":"10.1016/j.ibneur.2024.12.002","DOIUrl":"10.1016/j.ibneur.2024.12.002","url":null,"abstract":"<div><div>It is well recognized that type II Diabetes (T2D) and overweight/obesity are established risk factors for stroke, worsening also their consequences. However, the underlying mechanisms by which these disorders aggravate outcomes are not yet clear limiting the therapeutic opportunities. To fill this gap, we characterized, for the first time, the effects of T2D and obesity on the brain repair mechanisms occurring 7 days after stroke, notably glial scarring. In the present study, by performing a 30-minute middle cerebral artery occlusion (MCAO) on db/db (obese diabetics mice) and db/+ (controls) mice, we demonstrated that obese and diabetic mice displayed larger lesions (i.e. increased infarct volume, ischemic core, apoptotic cell number) and worsened neurological outcomes compared to their control littermates. We then investigated the formation of the glial scar in control and db/db mice 7 days post-stroke. Our observations argue in favor of a stronger and more persistent activation of astrocytes and microglia in db/db mice. Furthermore, an increased deposition of extracellular matrix (ECM) was observed in db/db vs control mice (i.e. chondroitin sulfate proteoglycan and collagen type IV). Consequently, we demonstrated for the first time that the db/db status is associated with increased astrocytic and microglial activation 7 days after stroke and resulted in higher deposition of ECM within the damaged area. Interestingly, the injury-induced neurogenesis appeared stronger in db/db as shown by the labeling of migrating neuroblast. This increase appeared correlated to the larger size of lesion. It nevertheless raises the question of the functional integration of the new neurons in db/db mice given the observed dense ECM, known to be repulsive for neuronal migration. Carefully limiting glial scar formation after stroke represents a promising area of research for reducing neuronal loss and limiting disability in diabetic/obese patients.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 16-30"},"PeriodicalIF":2.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004755","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":"Khat-induced conditioned place preference, extinction, and reinstatement in female mice","authors":"Caroline K. Murithi ,&nbsp;Jacques M. Kabaru ,&nbsp;Nilesh B. Patel","doi":"10.1016/j.ibneur.2024.11.015","DOIUrl":"10.1016/j.ibneur.2024.11.015","url":null,"abstract":"<div><div>Khat (<em>Catha edulis</em> Forsk), the natural source of cathinone and other psychoactive agents, is chewed by millions of persons in eastern Africa and the Arabian Peninsula for its psychostimulant effect. Using the conditioned place preference paradigm, this study tested fresh khat extract for place preference induction, extinction, and reinstatement. Female mice treated with 100 and 250 mg/kg of khat extract showed conditioned place preference, which was extinguished following a 16-day khat-free period. However, the place preference was reinstated following the first priming dose of the khat extract but not with the second priming dose done 35 days after the last conditioning treatment. The results show that khat has a rewarding/reinforcing property and can also lead to relapse behavior in persons attempting to stop khat use.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"18 ","pages":"Pages 1-5"},"PeriodicalIF":2.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093732","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":"Exploration of demographic prevalence of mild cognitive impairment using Montreal cognitive assessment: A cross-sectional pilot study in the Cape Coast Metropolis, Ghana.","authors":"David Larbi Simpong ,&nbsp;George Nkrumah Osei ,&nbsp;Richeal Odarko Mills ,&nbsp;Christopher Amaleyele Anyebem ,&nbsp;Benjamin Kofi Aikins ,&nbsp;Charlotte Gyanwaa Melfah ,&nbsp;Bridget Amoanimaa Osei ,&nbsp;Ansumana Bockarie","doi":"10.1016/j.ibneur.2024.11.008","DOIUrl":"10.1016/j.ibneur.2024.11.008","url":null,"abstract":"<div><h3>Background</h3><div>The Global prevalence of dementia is projected to rise, particularly in low and middle-income countries like Ghana. Mild cognitive impairment (MCI), an intermediate phase between normal cognitive aging and dementia, is characterized by an objective and subjective decline in cognitive abilities. Individuals with MCI have a greater likelihood of progression to dementia.</div></div><div><h3>Purpose</h3><div>There is a paucity of studies focused on assessing the prevalence, risk factors and characteristics of mild cognitive impairment within the Ghanaian population. This study assessed the prevalence of mild cognitive impairment and explored its relationship with various sociodemographic factors.</div></div><div><h3>Methods</h3><div>A prospective cross-sectional analytical study within Cape Coast, Ghana, evaluating the cognition of 100 participants using the Montreal Cognitive Assessment (MoCA) tool. The prevalence of MCI was determined using simple descriptive measures. The two-way ANOVA was used to determine risk factors for developing MCI. The Pearson correlation coefficient was used to determine the relationship between educational level and MoCA score.</div></div><div><h3>Results</h3><div>A majority (65.4 %) of participants within the age group 40–49 years had mild cognitive impairment. 42.86 % of male and 40.54 % of female participants had MCI (MoCA score &lt; 26). There was a significant correlation (r= 0.608, p= 0.0001) between the educational level of participants and the MoCA score. Participants classified as having MCI based on their MoCA score, performed significantly poorer in visuospatial, attention, language, abstraction and delayed recall domains compared to those with normal cognition.</div></div><div><h3>Conclusion</h3><div>The MoCA tool is a useful for detecting MCI, particularly among Ghanaians with at least 7 years of formal education. The prevalence of MCI among individuals aged 40–49 years in the Cape Coast Metropolis represents an important health burden.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"17 ","pages":"Pages 480-484"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881901","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":"Neuroprotective effects of Apigenin on prenatal Valproic acid-induced autism spectrum disorder in rats","authors":"Mitra Farbin ,&nbsp;Anahita Hejazi ,&nbsp;Nahid Fakhraei ,&nbsp;Yaser Azizi ,&nbsp;Soraya Mehrabi ,&nbsp;Razieh Hajisoltani","doi":"10.1016/j.ibneur.2024.10.003","DOIUrl":"10.1016/j.ibneur.2024.10.003","url":null,"abstract":"<div><div>Valproic acid (VPA) demonstrates teratogenic effects during pregnancy. Prenatal exposure to VPA may result in autism spectrum disorder (ASD) -like phenotypes. Apigenin, a natural flavonoid, has been shown to have neuroprotective impacts due to its antioxidant properties. This study aimed to investigate the protective effects of apigenin in prenatal Valproic acid-induced autism in rats. Female rats (220–240 g, 2–3 months) received a single dose of VPA (600 mg/kg, i.p.) on the 12.5th day of gestational. The male offspring were given oral apigenin (50 mg/kg, p.o.) or the vehicle for 30 days. Behavioral tests, biochemical assessments for oxidative stress markers and pro-inflammatory cytokines were performed. VPA-treated rats exhibited increased anxiety-like behavior, and repetitive behavior. Social interaction was reduced, and detection of the novel object was impaired. Also, VPA-treated rats have shown higher levels of oxidative stress malondialdehyde (MDA) and lower GPX and superoxide dismutase (SOD) levels. Furthermore, IL-6 and TNF-α increased in the prefrotalcortex decreased. On the other hand, apigenin-treated rats restored the cognitive consequences and lowered oxidative stress and inflammation in the prefrotalcortex.</div></div><div><h3>Conclusion</h3><div>Chronic apigenin treatment restored the behavioral and biochemical abnormalities caused by prenatal VPA exposure.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"17 ","pages":"Pages 493-502"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885817","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":"The role of SGK1 in neurologic diseases: A friend or foe?","authors":"Xiuze Chen ,&nbsp;Haixian Kang ,&nbsp;Yechen Xiao","doi":"10.1016/j.ibneur.2024.12.003","DOIUrl":"10.1016/j.ibneur.2024.12.003","url":null,"abstract":"<div><div>Serum and glucocorticoid-regulated kinase 1 (SGK1), a member of the AGC family of serine/threonine protein kinases, is one of the most conserved protein kinases in eukaryotic evolution. SGK1 is expressed to varying degrees in various types of cells throughout the body, and plays an important role in hypertension, ion channels, oxidative stress, neurological disorders, and cardiovascular regulation. In recent years, a number of scholars have devoted themselves to the study of the role and function of SGK1 in neurological diseases. Therefore, this article reviews the role of SGK1 in Alzheimer's disease, Parkinson's disease, epilepsy, stroke and other neurological diseases in recent years, and puts forward some insights on the role of SGK1 in neurological diseases and its relationship with disease activities.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"17 ","pages":"Pages 503-512"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906907","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":"Anticonvulsant effects of pentoxifylline on seizures induced by pentylenetetrazole and maximal electroshock in male mice: The role of the nitrergic pathway","authors":"Mohammad Keshavarzi ,&nbsp;Moein Ghasemi ,&nbsp;Mohammad Amin Manavi ,&nbsp;Ahmad Reza Dehpour ,&nbsp;Hamed Shafaroodi","doi":"10.1016/j.ibneur.2024.11.013","DOIUrl":"10.1016/j.ibneur.2024.11.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Epilepsy remains a challenge, with one-third of patients experiencing refractory seizures despite current anti-seizure medications. The nitrergic system, which involves nitric oxide (NO) and NO synthase (NOS) enzymes, plays a complex role in seizure pathophysiology. Pentoxifylline (PTPh), an FDA-approved phosphodiesterase inhibitor, has anticonvulsant effects; however, its relationship with the pathway is unclear. This study focused at how the nitrergic system could be involved in PTPh’s anticonvulsant effects.</div></div><div><h3>Methods</h3><div>Seizures were induced in male mice by intravenous pentylenetetrazole (PTZ) infusion (absence-like seizures), intraperitoneal PTZ injection, and maximal electroshock (generalized tonic-clonic seizures). PTPh was administered at various doses, alone or in combination with the NO precursor L-arginine, as well as non-selective (L-NAME) and selective NOS inhibitors (nNOS inhibitor 7-NI and iNOS inhibitor aminoguanidine). Seizure thresholds, latencies, incidence, and mortality were assessed. Moreover, in the next paradigm, using maximal electroshock model, we evaluate possible protective effects of PTPh against generalized tonic-clonic seizures and subsequent mortality.</div></div><div><h3>Results</h3><div>In the intravenous PTZ model, PTPh (≥150 mg/kg) increased the seizure threshold, potentiated by L-arginine but reduced by L-NAME and 7-nitroindazole. In the intraperitoneal PTZ model, 150 mg/kg PTPh decreased tonic seizure frequency, which was mitigated by aminoguanidine. However, PTPh failed to prolong clonic seizure latency. In the maximal electroshock test, 100 mg/kg PTPh protected against tonic seizure incidence (reduced by aminoguanidine). Although PTPh could not reduce mortality, its combination with L-NAME or 7-nitroindazole increased mortality compared with the vehicle-treated group.</div></div><div><h3>Conclusion</h3><div>PTPh exerted anticonvulsant effects against absence-like and generalized tonic-clonic seizures, likely through modulation of the nitrergic system involving neuronal, endothelial, and inducible NOS isoform. These findings provide novel insights into the complex interplay between NO signaling and the anticonvulsant actions of PTPh, highlighting the potential therapeutic implications of targeting the NO pathway in epilepsy management.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"17 ","pages":"Pages 485-492"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881899","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}