{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T15:01:35Z","timestamp":1785164495810,"version":"3.55.0"},"reference-count":79,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Funds","award":["UID\/06397\/2025"],"award-info":[{"award-number":["UID\/06397\/2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Adverse neurological events caused by imipenem are usually more frequent in patients with epilepsy. This study investigates the effects of imipenem on hippocampal neurogenesis, astroglial activation, and behaviour in animals with pro-epileptogenic alterations. Methods: Five-month-old Wistar rats were divided into four groups: control (CT), pentylenetetrazol (PTZ), imipenem-treated group (IM), and imipenem after PTZ-kindling (IM-PTZ). Epileptogenesis was induced by PTZ-kindling for 28 days, followed by 10 days of imipenem (40 mg\/kg) or saline injections. Rats underwent memory and anxiety tests followed by immunohistochemical analyses of doublecortin (DCX) and glial fibrillary acidic protein (GFAP) in the hippocampus. Results: Both kindled groups displayed comparable impairments in spatial learning and working memory, while imipenem alone did not alter behaviour. The IM-PTZ group failed to reach control-level performance only in the final Morris Water Maze acquisition trials, suggesting a deficit in memory consolidation rather than a total loss of retention, as the probe trial remained comparable across all groups. Although PTZ increased anxiety-like behaviour, no locomotor differences were observed in open-field test, confirming cognitive impairments were not due to motor deficits. These behavioural changes mirrored distinct cellular alterations: while PTZ alone triggered a compensatory increase in DCX neuronal density and astrocytic branching, imipenem co-administration suppressed this neurogenic response, bringing DCX to baseline. Furthermore, combined treatment induced an uncoupling of astrocytic response, marked by increased astrocyte density and reduced process complexity in dentate hilus and Cornus Ammonis 3 (CA3). Conclusions: These results suggest that imipenem modulates the cellular substrate of the pre-sensitized brain, interfering with hippocampal plasticity and glial compensatory mechanisms, rather than directly driving further behavioural deterioration.<\/jats:p>","DOI":"10.3390\/antibiotics15080728","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:08:14Z","timestamp":1785161294000},"page":"728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Imipenem on Cognitive Function, Anxiety-like Behaviour, Neurogenesis, and Astrogliosis in Pentylenetetrazol-Kindled Rats"],"prefix":"10.3390","volume":"15","author":[{"given":"Leonardo","family":"Ara\u00fajo-Andrade","sequence":"first","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"RISE-Health, Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Unidade Local de Sa\u00fade de S\u00e3o Jo\u00e3o\u2013Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3040-8854","authenticated-orcid":false,"given":"Pedro","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara","family":"Caetano-Mota","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"RISE-Health, Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuno","family":"Lima","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Silva","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"RISE-Health, Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2298-3143","authenticated-orcid":false,"given":"Pedro A.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"RISE-Health, Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0721-6547","authenticated-orcid":false,"given":"M. D.","family":"Madeira","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"RISE-Health, Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2967-6990","authenticated-orcid":false,"given":"Armando","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"RISE-Health, Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4943","DOI":"10.1128\/AAC.00296-11","article-title":"Carbapenems: Past, present, and future","volume":"55","author":"Endimiani","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1099\/jmm.0.001462","article-title":"JMM Profile: Carbapenems: A broad-spectrum antibiotic","volume":"70","author":"Armstrong","year":"2021","journal-title":"J. Med. Microbiol."},{"key":"ref_3","first-page":"895","article-title":"Imipenem\/cilastatin: The first carbapenem antibiotic","volume":"19","author":"Lyon","year":"1985","journal-title":"Drug Intell. Clin. Pharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1517\/14656566.9.1.23","article-title":"Carbapenems: A potent class of antibiotics","volume":"9","author":"Nicolau","year":"2008","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1128\/JCM.00298-16","article-title":"In Vitro Comparison of Ertapenem, Meropenem, and Imipenem against Isolates of Rapidly Growing Mycobacteria and Nocardia by Use of Broth Microdilution and Etest","volume":"54","author":"Killingley","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s10096-005-0021-y","article-title":"Neurotoxicity induced by beta-lactam antibiotics: From bench to bedside","volume":"24","author":"Chow","year":"2005","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_7","first-page":"1","article-title":"Neurotoxicity of beta-lactam antibiotics. Experimental kinetic and neurophysiological studies","volume":"55","author":"Schliamser","year":"1988","journal-title":"Scand. J. Infect. Dis. Suppl."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3014","DOI":"10.1111\/j.1476-5381.1995.tb15957.x","article-title":"Dual mechanisms of GABAA response inhibition by beta-lactam antibiotics in the pyramidal neurones of the rat cerebral cortex","volume":"116","author":"Fujimoto","year":"1995","journal-title":"Br. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S0749-0704(05)70367-5","article-title":"Antibiotic-induced convulsions","volume":"13","author":"Wallace","year":"1997","journal-title":"Crit. Care Clin."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/0378-4274(95)80008-2","article-title":"Correlation between in vitro and in vivo models of proconvulsive activity with the carbapenem antibiotics, biapenem, imipenem\/cilastatin and meropenem","volume":"76","author":"Day","year":"1995","journal-title":"Toxicol. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1592\/phco.31.4.408","article-title":"Epileptogenic Potential of Carbapenem Agents: Mechanism of Action, Seizure Rates, and Clinical Considerations","volume":"31","author":"Miller","year":"2011","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1093\/jac\/dkx209","article-title":"Too much of a good thing: A retrospective study of \u03b2-lactam concentration\u2013toxicity relationships","volume":"72","author":"Imani","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1097\/INF.0b013e31828be70b","article-title":"Adverse Events Associated With Meropenem Versus Imipenem\/Cilastatin Therapy in a Large Retrospective Cohort of Hospitalized Infants","volume":"32","author":"Hornik","year":"2013","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_14","first-page":"240","article-title":"Cell Type Specificity of GABAA Receptor Mediated Signaling in the Hippocampus. Current drug targets","volume":"2","author":"Semyanov","year":"2003","journal-title":"CNS Neurol. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1101\/lm.134706","article-title":"Reversible hippocampal lesions disrupt water maze performance during both recent and remote memory tests","volume":"13","author":"Broadbent","year":"2006","journal-title":"Learn. Mem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0165-3806(84)90046-4","article-title":"Penicillin-induced epileptogenesis in immature rat CA3 hippocampal pyramidal cells","volume":"314","author":"Swann","year":"1984","journal-title":"Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e24942","DOI":"10.1002\/jcla.24942","article-title":"New findings about comparing the effects of antibiotic therapy and phage therapy on memory and hippocampal pyramidal cells in rats","volume":"37","author":"Darbandi","year":"2023","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1046\/j.1528-1157.2001.34701.x","article-title":"Seizures in the Critically Ill: The Role of Imipenem","volume":"42","author":"Koppel","year":"2001","journal-title":"Epilepsia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1093\/jac\/dku111","article-title":"The risk of seizures among the carbapenems: A meta-analysis","volume":"69","author":"Cannon","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3923\/pjbs.2013.151.159","article-title":"Hippocampus and cerebellum function following imipenem treatment in male and female rats: Evaluation of sex differences during developmental stage","volume":"16","author":"Golchin","year":"2013","journal-title":"Pak. J. Biol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/jac\/20.3.413","article-title":"Penetration of imipenem and other antibiotics into inflammatory exudate and their efficacy in pseudomonas infection in the rat granuloma pouch model","volume":"20","author":"Hashizume","year":"1987","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/516284","article-title":"Pharmacokinetic\/pharmacodynamic parameters: Rationale for antibacterial dosing of mice and men","volume":"26","author":"Craig","year":"1998","journal-title":"Clin. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.2165\/00003495-200767070-00006","article-title":"Comparative review of the carbapenems","volume":"67","author":"Zhanel","year":"2007","journal-title":"Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1128\/AAC.50.1.34-37.2006","article-title":"Microdialysis Study of Imipenem Distribution in the Intraperitoneal Fluid of Rats with or without Experimental Peritonitis","volume":"50","author":"Lefeuvre","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9.37.1","DOI":"10.1002\/0471142301.ns0937s58","article-title":"Pentylenetetrazol (PTZ) kindling model of epilepsy","volume":"58","author":"Dhir","year":"2012","journal-title":"Curr. Protoc. Neurosci."},{"key":"ref_26","first-page":"56573","article-title":"Pentylenetetrazole-Induced Kindling Mouse Model","volume":"136","author":"Shimada","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/S0022-3565(24)29466-0","article-title":"Pentylenetetrazole-induced inhibition of recombinant gamma-aminobutyric acid type A (GABA(A)) receptors: Mechanism and site of action","volume":"298","author":"Huang","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1007\/s11011-021-00823-3","article-title":"PTZ kindling model for epileptogenesis, refractory epilepsy, and associated comorbidities: Relevance and reliability","volume":"36","author":"Singh","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1006\/ebeh.2000.0085","article-title":"Consequences of Pentylenetetrazole Kindling on Spatial Memory and Emotional Responding in the Rat","volume":"1","author":"Lamberty","year":"2000","journal-title":"Epilepsy Behav."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"106534","DOI":"10.1016\/j.eplepsyres.2020.106534","article-title":"Effects of ketogenic diet on cognitive function in pentylenetetrazol-kindled rats","volume":"170","author":"Wang","year":"2021","journal-title":"Epilepsy Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Liu, X., Wu, Y., Huang, Q., Zou, D., Qin, W., and Chen, Z. (2015). Grouping Pentylenetetrazol-Induced Epileptic Rats According to Memory Impairment and MicroRNA Expression Profiles in the Hippocampus. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126123"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0304-3940(91)90302-A","article-title":"Changes in seizure latency correlate with alterations in A1 adenosine receptor binding during daily repeated pentylentetrazol-induced convulsions in different mouse brain areas","volume":"132","author":"Angelatou","year":"1991","journal-title":"Neurosci. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hoeller, A.A., De Carvalho, C.R., Franco, P.L.C., Formolo, D.A., Imthon, A.K., Dos Santos, H.R., Eidt, I., Souza, G.R., Constantino, L.C., and Ferreira, C.L. (2017). Behavioral and Neurochemical Consequences of Pentylenetetrazol-Induced Kindling in Young and Middle-Aged Rats. Pharmaceuticals, 10.","DOI":"10.3390\/ph10030075"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s10072-011-0561-0","article-title":"Memantine attenuates the impairment of spatial learning and memory of pentylenetetrazol-kindled rats","volume":"32","author":"Jia","year":"2011","journal-title":"Neurol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.physbeh.2016.04.028","article-title":"Prediction of seizure incidence probability in PTZ model of kindling through spatial learning ability in male and female rats","volume":"161","author":"Haeri","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/nprot.2006.116","article-title":"Morris water maze: Procedures for assessing spatial and related forms of learning and memory","volume":"1","author":"Vorhees","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e3162","DOI":"10.21769\/BioProtoc.3162","article-title":"Assessing Spatial Working Memory Using the Spontaneous Alternation Y-maze Test in Aged Male Mice","volume":"9","author":"Prieur","year":"2019","journal-title":"Bio Protoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7809","DOI":"10.1523\/JNEUROSCI.22-17-07809.2002","article-title":"Conceptual, Spatial, and Cue Learning in the Morris Water Maze in Fast or Slow Kindling Rats: Attention Deficit Comorbidity","volume":"22","author":"Anisman","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_39","first-page":"51","article-title":"Effects of pentylenetetrazol-induced kindling on mature and immature rat behavior, emotional learning and levels of nitric oxide in brain and serum","volume":"25","author":"Kanan","year":"2018","journal-title":"J. Turk. Epilepsi Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1093\/jpp\/rgad022","article-title":"Tetramethylpyrazine contributes to the neuroprotection in a rodent epileptic model of pentylenetetrazole-induced kindling","volume":"75","author":"Danduga","year":"2023","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110019","DOI":"10.1016\/j.yebeh.2024.110019","article-title":"Dynamic changes in seizure state and anxiety-like behaviors during pentylenetetrazole kindling in rats","volume":"159","author":"Kajita","year":"2024","journal-title":"Epilepsy Behav."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0896-6273(00)80778-3","article-title":"Doublecortin Is a Microtubule-Associated Protein and Is Expressed Widely by Migrating Neurons","volume":"23","author":"Gleeson","year":"1999","journal-title":"Neuron"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"a018812","DOI":"10.1101\/cshperspect.a018812","article-title":"Neurogenesis in the Adult Hippocampus","volume":"7","author":"Kempermann","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.neuroscience.2004.10.009","article-title":"A role for adult neurogenesis in spatial long-term memory","volume":"130","author":"Snyder","year":"2005","journal-title":"Neuroscience"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.cell.2008.01.033","article-title":"Mechanisms and functional implications of adult neurogenesis","volume":"132","author":"Zhao","year":"2008","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Pl\u00fcmpe, T., Ehninger, D., Steiner, B., Klempin, F., Jessberger, S., Brandt, M., R\u00f6mer, B., Rodriguez, G.R., Kronenberg, G., and Kempermann, G. (2006). Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation. BMC Neurosci., 7.","DOI":"10.1186\/1471-2202-7-77"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Buga, A.-M., Vintilescu, R., Balseanu, A.T., Pop, O.T., Streba, C., Toescu, E., and Popa-Wagner, A. (2012). Repeated PTZ Treatment at 25-Day Intervals Leads to a Highly Efficient Accumulation of Doublecortin in the Dorsal Hippocampus of Rats. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039302"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1177\/1535759719868186","article-title":"Adult Neurogenesis in the Development of Epilepsy","volume":"19","author":"Danzer","year":"2019","journal-title":"Epilepsy Curr."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ara\u00fajo-Andrade, L., Caetano-Mota, B., Silva, I., Rogeiro, A., Nogueira, P., Silva, A., Pereira, P.A., Madeira, M.D., and Cardoso, A. (2026). Imipenem in the Rat Brain: A Multidimensional Study on Hippocampal Behavior, GABAergic System, Astrocyte Response, and Neurogenesis. Antibiotics, 15.","DOI":"10.3390\/antibiotics15020218"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.seizure.2020.08.012","article-title":"Antibiotic-induced epileptic seizures: Mechanisms of action and clinical considerations","volume":"81","author":"Wanleenuwat","year":"2020","journal-title":"Seizure"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.pnpbp.2003.09.026","article-title":"Anticonvulsant and antiepileptogenic effects of GABAA receptor ligands in pentylenetetrazole-kindled mice","volume":"28","author":"Hansen","year":"2004","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S0896-6273(00)80907-1","article-title":"Interactions between distinct GABA(A) circuits in hippocampus","volume":"25","author":"Banks","year":"2000","journal-title":"Neuron"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nrn.2016.21","article-title":"Rhythms of the hippocampal network","volume":"17","author":"Colgin","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3389\/neuro.01.010.2008","article-title":"Relationship of hippocampal theta and gamma oscillations to potentiation of synaptic transmission","volume":"2","author":"Bikbaev","year":"2008","journal-title":"Front. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.freeradbiomed.2016.03.004","article-title":"NADPH oxidase activation is required for pentylenetetrazole kindling-induced hippocampal autophagy","volume":"94","author":"Zhu","year":"2016","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.jocn.2005.10.018","article-title":"Enhanced hippocampal neurodegeneration after traumatic or kainate excitotoxicity in GFAP-null mice","volume":"13","author":"Otani","year":"2006","journal-title":"J. Clin. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"38108","DOI":"10.1038\/srep38108","article-title":"Remarkable alterations of Nav1.6 in reactive astrogliosis during epileptogenesis","volume":"6","author":"Zhu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Postnikova, T.Y., Trofimova, A.M., Zakharova, M.V., Nosova, O.I., Brazhe, A.R., Korzhevskii, D.E., Semyanov, A.V., and Zaitsev, A.V. (2022). Delayed Impairment of Hippocampal Synaptic Plasticity after Pentylenetetrazole-Induced Seizures in Young Rats. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113461"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/glia.20207","article-title":"Astrocyte activation and reactive gliosis","volume":"50","author":"Pekny","year":"2005","journal-title":"Glia"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41593-020-00783-4","article-title":"Reactive astrocyte nomenclature, definitions, and future directions","volume":"24","author":"Escartin","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40478-023-01526-9","article-title":"Roles of neuropathology-associated reactive astrocytes: A systematic review","volume":"11","author":"Lawrence","year":"2023","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00401-019-01980-7","article-title":"The contribution of astrocytes to the neuroinflammatory response in multiple sclerosis and experimental autoimmune encephalomyelitis","volume":"137","author":"Brambilla","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Zhang, H., Zhang, X., Chai, Y., Wang, Y., Zhang, J., and Chen, X. (2025). Astrocyte-mediated inflammatory responses in traumatic brain injury: Mechanisms and potential interventions. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1584577"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.4103\/1673-5374.306064","article-title":"Astrocytes: A double-edged sword in neurodegenerative diseases","volume":"16","author":"Ding","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1002\/glia.22312","article-title":"Astrocyte immune responses in epilepsy","volume":"60","author":"Aronica","year":"2012","journal-title":"Glia"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.bbi.2013.05.011","article-title":"A cytokine network involving brain-borne IL-1\u03b2, IL-1ra, IL-18, IL-6, and TNF\u03b1 operates during long-term potentiation and learning","volume":"33","author":"Balschun","year":"2013","journal-title":"Brain Behav. Immun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8914","DOI":"10.3390\/cimb46080527","article-title":"Neuroprotective Effects of Myricetin on PTZ-Induced Seizures in Mice: Evaluation of Oxidation, Neuroinflammation and Metabolism, and Apoptosis in the Hippocampus","volume":"46","author":"Demyashkin","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12974-016-0572-0","article-title":"Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice","volume":"13","author":"Couch","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1007\/s00213-016-4218-9","article-title":"Stress and neuroinflammation: A systematic review of the effects of stress on microglia and the implications for mental illness","volume":"233","author":"Calcia","year":"2016","journal-title":"Psychopharmacology"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Escalada, P., Ezkurdia, A., Ram\u00edrez, M.J., and Solas, M. (2024). Essential Role of Astrocytes in Learning and Memory. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031899"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Liu, J., Si, Z., Li, S., Huang, Z., He, Y., Zhang, T., and Wang, A. (2018). The Calcineurin Inhibitor FK506 Prevents Cognitive Impairment by Inhibiting Reactive Astrogliosis in Pilocarpine-Induced Status Epilepticus Rats. Front. Cell. Neurosci., 11.","DOI":"10.3389\/fncel.2017.00428"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0361-9230(96)00176-1","article-title":"Comparison Among Different Approaches for Sampling Cerebrospinal Fluid in Rats","volume":"41","author":"Huang","year":"1996","journal-title":"Brain Res. Bull."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0361-9230(91)90083-V","article-title":"Changes in physiological parameters of rat cerebrospinal fluid during chronic sampling: Evaluation of two sampling methods","volume":"27","author":"Irena","year":"1991","journal-title":"Brain Res. Bull."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0013-4694(72)90177-0","article-title":"Modification of seizure activity by electrical stimulation. II. Motor seizure","volume":"32","author":"Racine","year":"1972","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e70020","DOI":"10.1002\/cpz1.70020","article-title":"Kindling Models of Epileptogenesis for Developing Disease-Modifying Drugs for Epilepsy","volume":"4","author":"Reddy","year":"2024","journal-title":"Curr. Protoc."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0006-8993(87)91557-5","article-title":"Asymmetry in the hippocampal region specific for one of two closely related species of wild mice","volume":"436","author":"Slomianka","year":"1987","journal-title":"Brain Res."},{"key":"ref_77","unstructured":"Paxinos, G., and Watson, C. (2006). The Rat Brain in Stereotaxic Coordinates: Hard Cover Edition, Elsevier."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0301-0082(89)90009-9","article-title":"Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region","volume":"33","author":"Witter","year":"1989","journal-title":"Prog. Neurobiol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Marques, S.I., Carmo, H., Carvalho, F., S\u00e1, S.I., and Silva, J.P. (2023). A Semi-Automatic Method for the Quantification of Astrocyte Number and Branching in Bulk Immunohistochemistry Images. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054508"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/8\/728\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:31:25Z","timestamp":1785162685000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/8\/728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":79,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["antibiotics15080728"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15080728","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]}}}