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Topiramate in Refractory Status Epilepticus: A Systematic Review 2 2 Epilepsy is a chronic neurological disease characterized by recurrent seizures and is caused by abnormal electrical activity in neuronal circuits. Refractory status epilepticus is a life-threatening condition that does not respond to first- and second-line anticonvulsant medications. Topiramate is a powerful antiseizure medication that is used in various types of epilepsy. This study aimed to investigate the effect of topiramate in treatment of refractory status epilepticus. We have developed search strategies to identify articles related to the effect of topiramate on refractory status epilepticus. Our searches encompassed validated databases, including PubMed / MEDLINE, Scopus, Google Scholar and Cochrane Library, from 2012 to May 2026. Of the 896 articles found in the preliminary search, 10 clinical studies were selected for structured review.  The results of this study showed that refractory status epilepticus occurs in about 38% of patients with status epilepticus and causes more mortality and disability. Acute symptomatic seizures tend to be resistant to treatment. Topiramate treatment ameliorated epileptic seizures in 194 cases out of 317 patients. Adverse effects, including pancreatitis and metabolic acidosis, and allergic reactions have been reported in rare cases. In conclusion, the available evidence suggests that topiramate may be a potentially useful adjunctive therapy for refractory status epilepticus, especially when administered early. However, reported studies are limited and most of them are based on observational data. Further well-designed prospective studies are required to evaluate its efficacy and safety. 0 0 2025/09/8 1404/6/17 2026/07/11 1405/4/20 Hamideh Arvan Hamideh Arvan Kerman University of Medical Sciences hamide.md62@gmail.com Asieh Mehramiri Asieh Mehramiri Ahvaz Jundishapur University of Medical Sciences mehramiri.ac@gmail.com Mitra Ansari Dezfouli Mitra Ansari Dezfouli Ahvaz Jundishapur University of Medical Sciences mitraansari84@gmail.com Topiramate Refractory Status Epilepticus Epilepsy Seizures Akyıldız B N, Kumandaş S. Treatment of pediatric refractory status epilepticus with topiramate. Child's Nervous System 2011; 27: 1425-1430.##Asadi-Pooya A A, Jahromi M J, Izadi S, Emami Y. Treatment of refractory generalized convulsive status epilepticus with enteral topiramate in resource limited settings. Seizure 2015; 24: 114-117.##Au Y K, Kananeh M F, Rahangdale R, Moore T E, Panza G A, Gaspard N, et al. Treatment of refractory status epilepticus with continuous intravenous anesthetic drugs: a systematic review. JAMA neurology 2024; 81: 534-548.##Bai Y-F, Zeng C, Jia M, Xiao B. Molecular mechanisms of topiramate and its clinical value in epilepsy. Seizure 2022; 98: 51-56.##Besli G E, Karatoprak E Y, Yilmaz S. Efficacy and safety profile of intravenous levetiracetam versus phenytoin in convulsive status epilepticus and acute repetitive seizures in children. Epilepsy & Behavior 2020; 111: 107289.##Brigo F, Bragazzi N L, Igwe S C, Nardone R, Trinka E. Topiramate in the treatment of generalized convulsive status epilepticus in adults: a systematic review with individual patient data analysis. Drugs 2017; 77: 67-74.##Brigo F, Del Giovane C, Nardone R, Trinka E, Lattanzi S. Intravenous antiepileptic drugs in adults with benzodiazepine-resistant convulsive status epilepticus: a systematic review and network meta-analysis. Epilepsy & Behavior 2019; 101: 106466.##Chimakurthy A K, Ramsay R E, Sabharwal V, Menon U. Safety, tolerability, and pharmacokinetics of weight-based IV loading dose of lacosamide in the ICU. Epilepsy & Behavior 2021; 114: 107449.##Cock H R, Group E. Established status epilepticus treatment trial (ESETT). Epilepsia 2011; 52: 50-52.##Fariba K A, Saadabadi A. Topiramate. StatPearls [Internet]: StatPearls Publishing, 2024.##Fechner A, Hubert K, Jahnke K, Knake S, Konczalla J, Menzler K, et al. Treatment of refractory and superrefractory status epilepticus with topiramate: a cohort study of 106 patients and a review of the literature. Epilepsia 2019; 60: 2448-2458.##Fisher R S, Cross J H, French J A, Higurashi N, Hirsch E, Jansen F E, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58: 522-530.##Hakami T. Efficacy and tolerability of antiseizure drugs. 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Enteral topiramate treatment in refractory status epilepticus. Epilepsy Research 2025; 213: 107551.##Klowak J A, Hewitt M, Catenacci V, Duffett M, Rochwerg B, Jones K, Choong K. Levetiracetam versus phenytoin or fosphenytoin for second-line treatment of pediatric status epilepticus: a meta-analysis. Pediatric Critical Care Medicine 2021; 22: e480-e491.##Kortland L M, Alfter A, Bähr O, Carl B, Dodel R, Freiman T M, et al. Costs and cost‐driving factors for acute treatment of adults with status epilepticus: a multicenter cohort study from Germany. Epilepsia 2016; 57: 2056-2066.##Lim S-N, Wu T, Tseng W-E J, Chiang H-I, Cheng M-Y, Lin W-R, Lin C-N. Efficacy and safety of perampanel in refractory and super-refractory status epilepticus: cohort study of 81 patients and literature review. Journal of Neurology 2021: 1-14.##Löscher W, Soul J S. Topiramate for the treatment of neonatal seizures and beyond. Epilepsia 2025.##Madžar D, Kuramatsu J B, Gerner S T, Huttner H B. Assessing the value of topiramate in refractory status epilepticus. Seizure 2016; 38: 7-10.##Niquet J, Lumley L, Baldwin R, Rossetti F, Schultz M, de Araujo Furtado M, et al. Early polytherapy for benzodiazepine-refractory status epilepticus. Epilepsy & Behavior 2019; 101: 106367.##Orlandi N, Bartolini E, Audenino D, Moja M C, Urso L, d'Orsi G, et al. Intravenous brivaracetam in status epilepticus: a multicentric retrospective study in Italy. Seizure 2021; 86: 70-76.##Orlandi N, Gozzi A, Giovannini G, Turchi G, Cioclu M C, Vaudano A E, Meletti S. Recurrent status epilepticus: Clinical features and recurrence risk in an adult population. Seizure 2022; 97: 1-7.##Panda P K, Panda P, Dawman L, Sharawat I K. Efficacy of lacosamide and phenytoin in status epilepticus: A systematic review. Acta Neurologica Scandinavica 2021; 144: 366-374.##Rohracher A, Kellinghaus C, Strzelczyk A. Topiramate, perampanel and brivaracetam in status epilepticus: How should they be used and what effect can be expected? Zeitschrift für Epileptologie 2018; 31: 256-261.##Rosenthal E S, Claassen J, Wainwright M S, Husain A M, Vaitkevicius H, Raines S, et al. Brexanolone as adjunctive therapy in super‐refractory status epilepticus. Annals of neurology 2017; 82: 342-352.##Santamarina E, Parejo Carbonell B, Sala J, Gutiérrez‐Viedma Á, Miró J, Asensio M, et al. Use of intravenous brivaracetam in status epilepticus: a multicenter registry. Epilepsia 2019; 60: 1593-1601.##Sarangi S C, Kakkar A K, Kumar R, Gupta Y K. Effect of lamotrigine, levetiracetam & topiramate on neurobehavioural parameters & oxidative stress in comparison with valproate in rats. Indian Journal of Medical Research 2016; 144: 104-111.##Scheffer I E, Berkovic S, Capovilla G, Connolly M B, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Zeitschrift für Epileptologie 2018; 31: 296-306.##Schubert‐Bast S, Zöllner J P, Ansorge S, Hapfelmeier J, Bonthapally V, Eldar‐Lissai A, et al. Burden and epidemiology of status epilepticus in infants, children, and adolescents: a population‐based study on German health insurance data. Epilepsia 2019; 60: 911-920.##Shishmanova-Doseva M, Peychev L, Yoanidu L, Uzunova Y, Atanasova M, Georgieva K, Tchekalarova J. Anticonvulsant effects of topiramate and lacosamide on pilocarpine-induced status epilepticus in rats: a role of reactive oxygen species and inflammation. International Journal of Molecular Sciences 2021; 22: 2264.##Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain 2011; 134: 2802-2818.##Stojanova V, Rossetti A. Oral topiramate as an add‐on treatment for refractory status epilepticus. Acta Neurologica Scandinavica 2012; 125: e7-e11.##Suttichaimongkol T, Tiamkao S, Sawanyawisuth K. The efficacy of topiramate in status epilepticus, experience from Thailand. Neurology Asia 2012; 17.##Synowiec A S, Yandora K A, Yenugadhati V, Valeriano J P, Schramke C J, Kelly K M. The efficacy of topiramate in adult refractory status epilepticus: experience of a tertiary care center. Epilepsy research 2012; 98: 232-237.##Tanaka T, Ihara M, Fukuma K, Mishra N K, Koepp M J, Guekht A, Ikeda A. Pathophysiology, diagnosis, prognosis, and prevention of poststroke epilepsy: clinical and research implications. Neurology 2024; 102: e209450.##Tantikittichaikul S, Johnson J, Laengvejkal P, DeToledo J. Topiramate-induced hyperammonemic encephalopathy in a patient with mental retardation: a case report and review of the literature. Epilepsy & behavior case reports 2015; 4: 84-85.##Tarulli A, Drislane F W. The use of topiramate in refractory status epilepticus. Neurology 2004; 62: 837-837.##Welling L C, Rabelo N N, Yoshikawa M H, Telles J P M, Teixeira M J, Figueiredo E G. Efficacy of topiramate as an add-on therapy in patients with refractory status epilepticus: a short systematic review. Revista Brasileira de terapia intensiva 2021; 33: 440-444.##Zhang Y, Liu Y, Liao Q, Liu Z. Preferential antiseizure medications in pediatric patients with convulsive status epilepticus: a systematic review and network meta-analysis. Clinical Drug Investigation 2021; 41: 1-17.## ##

Identification of Drug Targets and Their Candidate Drugs in Multiple Sclerosis and Bipolar Disorder via Systems Biology Approach 2 2 Introduction: Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination of the central nervous system. Bipolar Disorder (BD) is a complex psychiatric condition. Patients with MS have a significantly elevated risk of developing BD. The present study aimed to investigate the shared genetic mechanisms between MS-BD using systems biology approaches. Methods: We constructed a protein-protein interaction (PPI) network of the overlapping MS-BD genes using the STRING database and identified functional modules and hub genes with Cytoscape. Gene ontology and pathway enrichment analyses of the modules and hub genes were performed using g:Profiler. Potential drug targets among these genes were further explored using DGIdb. Results: A total of 206 genes associated with MS and 201 genes associated with BD were retrieved from the NCBI, of which 55 genes were common to both diseases. PPI network analysis revealed ten functional modules. Ten hub genes -TNF, IL6, IL1B, TLR4, AKT1, BCL2, IFNG, APP, NFKB1, and MTOR- were identified as central players in both conditions. TNF and IL6 showed upregulated expression in MS-BD and emerged as promising drug targets. The enriched KEGG pathways included tuberculosis, HIF-1 signaling, AGE-RAGE signaling in diabetic complications, and the Toll-like receptor signaling pathway. Conclusion: Our findings highlight the shared biological processes and gene expression patterns between MS-BD. These results suggest that MS-BD may involve common underlying mechanisms, which could open new avenues for repurposing existing drugs and developing combined therapeutic strategies. Such insights may ultimately improve prevention and treatment approaches for MS-BD, as well as related comorbidities. 0 0 2025/09/82025/09/20 1404/6/29 2026/07/112026/07/22 1405/4/31 Shahang Shamshiri Shahang Shamshiri Faculty of Mathematics and Computer Science, Department of Applied Mathematics, Shahid Bahonar University, Kerman, IranBahonar Bioinformatics Lab (BBL), Kerman, Iran Shahang.sh@gmail.com Shahedeh Shamshiri Shahedeh Shamshiri Faculty of Mathematics and Computer Science, Department of Applied Mathematics, Shahid Bahonar University, Kerman, IranBahonar Bioinformatics Lab (BBL), Kerman, Iran Shahandeshamshiri@gmail.com Behjat Kalantari-Khandani Behjat Kalantari-Khandani Department of Oncology School of Medicine, Kerman University of Medical Sciences, Kerman, Iran b_kalantari@kmu.ac.ir Mohammad-Javad Niazi Mohammad-Javad Niazi Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran Bahonar Bioinformatics Lab (BBL), Kerman, Iran niazimohamadjavad@gmail.com Zahra Ziaastani Zahra Ziaastani Faculty of Mathematics and Computer Science, Department of Applied Mathematics, Shahid Bahonar University, Kerman, IranBahonar Bioinformatics Lab (BBL), Kerman, Iran zahraziaastani@gmail.com Ali Kazemipour Ali Kazemipour Faculty of Mathematics and Computer Science, Department of Applied Mathematics, Shahid Bahonar University, Kerman, IranBahonar Bioinformatics Lab (BBL), Kerman, Iran ali.kazemi@uk.ac.ir Multiple Sclerosis Bipolar Disorder PPI network Drug Target Identification Systems Biology 1. 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Mechanistic insights into the effects of SGLT2 inhibitors on cardiovascular dysfunction in heart failure: a preclinical narrative review 2 2 Heart failure (HF) remains a major global health challenge, particularly among aging populations and patients with type 2 diabetes (T2D). Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally developed as glucose-lowering agents, have demonstrated significant cardiovascular benefits in patients with HF regardless of diabetic status.The reviewed studies indicate that SGLT2 inhibitors may exert cardioprotective effects through the attenuation of oxidative stress, inflammation, mitochondrial dysfunction, apoptosis, and cardiac fibrosis. Several studies have shown that modulation of signaling pathways involving NADPH oxidases, Sirtuin 1, AMPK, and STAT3 contributes to reducing myocardial injury and adverse cardiac remodeling. These findings suggest that the cardiovascular benefits of SGLT2 inhibitors extend beyond glycemic control and may directly influence molecular pathways involved in HF progression. In conclusion, the reviewed evidence suggests that SGLT2 inhibitors play an important role in attenuating oxidative stress, improving cardiac function, and slowing the progression of heart failure through multiple cardioprotective mechanisms. These findings also highlight the SGLT2 inhibitors may have potential implications for the prevention of cardiovascular diseases and provide important directions for future research.   0 0 2025/09/82025/09/202025/08/3 1404/5/12 2026/07/112026/07/222026/07/26 1405/5/4 Paniz Negareshifard Paniz Negareshifard School of medicine, Semnan University of Medical Sciences, Semnan, Iran paniznegareshi00@gmail.com Saeedeh Keshavarzi Saeedeh Keshavarzi School of medicine, Semnan University of Medical Sciences, Semnan, Iran saeedehkeshavarzi97@gmail.com Anoosha Habibian Anoosha Habibian School of medicine, Semnan University of Medical Sciences, Semnan, Iran Anooshahabibian@gmail.com Kosar Bagheriha Kosar Bagheriha School of medicine, Semnan University of Medical Sciences, Semnan, Iran Kbagheriha@gmail.com Seyedeh Zahra Banihashemian Seyedeh Zahra Banihashemian School of medicine, Semnan University of Medical Sciences, Semnan, Iran seyedehzahra.banihashemian@gmail.com Bahador Bagheri Bahador Bagheri Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran bahadordvm@yahoo.com Marzieh Noruzi Marzieh Noruzi School of pharmacy, Semnan University of Medical Sciences, Semnan, Iran. marziyehnoruzi@semums.ac.ir Heart failure SGLT2 inhibitor oxidative stress cardioprotective Andreadou, I., Efentakis, P., Balafas, E., Togliatto, G., Davos, C. 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Chemotherapy-Induced Hippocampal Neurodegeneration: A Focus on Alkylating Agents and the Role of miR-204 2 2 Introduction: The molecular mechanisms underlying chemotherapy-associated hippocampal neurodegeneration, particularly following exposure to alkylating agents, remain poorly understood. This study investigated the association between melphalan- and chlorambucil-induced hippocampal injury and alterations in apoptosis-, autophagy-, and miR-204-related pathways. Methods: Adult male Wistar rats were treated daily for 30 days with saline (control), Mel, or Chl. Hippocampal tissue was analyzed using histological assessment of dark neurons and qRT-PCR analysis of apoptosis-related genes (Bax, Bcl-2, Caspase-3), autophagy-related genes (LC3β and Beclin-1), and miR-204 expression. Results: Both Mel and Chl significantly increased the density of dark neurons in the hippocampus compared with the control group. Molecular analysis revealed increased expression of the pro-apoptotic genes BAX and Caspase-3 together with reduced expression of the anti-apoptotic gene BCL2. In addition, the expression levels of the autophagy-related genes LC3β and Beclin-1 were significantly decreased following treatment. Furthermore, miR-204 expression was significantly upregulated in both Mel and Chl groups and was associated with hippocampal neurodegeneration, increased expression of apoptosis-related genes, and reduced expression of autophagy-related genes. Conclusion: These findings indicate that systemic exposure to melphalan and chlorambucil is associated with hippocampal neurodegenerative changes accompanied by altered expression of apoptosis- and autophagy-related genes. The consistent upregulation of miR-204 suggests that this microRNA may contribute to alkylating agent-associated hippocampal neurodegeneration; however, further functional studies are required to determine its mechanistic role and therapeutic relevance in chemotherapy-related cognitive impairment. 0 0 2025/09/82025/09/202025/08/32026/05/4 1405/2/14 2026/07/112026/07/222026/07/262026/08/5 1405/5/14 Amirhossein Ebadi Amirhossein Ebadi Student Research Committee, Gonabad University of Medical Sciences, Gonabad, IR Iran. ebadi.amirhossein0282@yahoo.com maryam moghimian maryam moghimian Department of Physiology, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, IR Iran moghimian2@yahoo.com Samira eyzi Samira eyzi Department of Anatomy, School of Medicine, Gonabad University of Medical Sciences, Gonabad, IR Iran eziysamira@gmail.com zahra saadatian zahra saadatian Department of Physiology, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, IR Iran z.saadatian@yahoo.com Vida Alikhani Vida Alikhani Department of Physiology, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, IR Iran vd.alikhani@gmail.com malihe soltani malihe soltani Malihe Soltani, Associate Professor, Department of Anatomy, School of Medicine, Gonabad University of Medical Sciences, Gonabad, IR Iran soltanimalihe@yahoo.com Hippocampal Neurodegeneration Melphalan Chlorambucil microRNA-204 REFERENCES##Alhowail A, Aldubayan M. 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