{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T13:31:01Z","timestamp":1781530261347,"version":"3.54.1"},"reference-count":56,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"#NEXTGENERATIONEU and the Italian Ministry of University and Research, National Recovery and Resilience Plan (PNRR)","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"#NEXTGENERATIONEU and the Italian Ministry of University and Research, National Recovery and Resilience Plan (PNRR)","award":["2022-ID52251-2022.0087"],"award-info":[{"award-number":["2022-ID52251-2022.0087"]}]},{"name":"Fondazione Cariverona-Bando Ricerca e Sviluppo","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"Fondazione Cariverona-Bando Ricerca e Sviluppo","award":["2022-ID52251-2022.0087"],"award-info":[{"award-number":["2022-ID52251-2022.0087"]}]},{"name":"Excellence Project 2023\u20132027 of the Department of Neuroscience, Biomedicine and Movement Sciences of the University of Verona, funded by Italian Ministry of University and Research","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"name":"Excellence Project 2023\u20132027 of the Department of Neuroscience, Biomedicine and Movement Sciences of the University of Verona, funded by Italian Ministry of University and Research","award":["2022-ID52251-2022.0087"],"award-info":[{"award-number":["2022-ID52251-2022.0087"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>In animal models of epilepsy, cranial surgery is often required to implant electrodes for electroencephalography (EEG) recording. However, electrode implants can lead to the activation of glial cells and interfere with physiological neuronal activity. In this study, we evaluated the impact of epidural electrode implants in the pilocarpine mouse model of temporal lobe epilepsy. Brain neuroinflammation was assessed 1 and 3 weeks after surgery by cytokines quantification, immunohistochemistry, and western blotting. Moreover, we investigated the effect of pilocarpine, administered two weeks after surgery, on mice mortality rate. The reported results indicate that implanted mice suffer from neuroinflammation, characterized by an early release of pro-inflammatory cytokines, microglia activation, and subsequent astrogliosis, which persists after three weeks. Notably, mice subjected to electrode implants displayed a higher mortality rate following pilocarpine injection 2 weeks after the surgery. Moreover, the analysis of EEGs recorded from implanted mice revealed a high number of single spikes, indicating a possible increased susceptibility to seizures. In conclusion, epidural electrode implant in mice promotes neuroinflammation that could lower the seizure thresholds to pilocarpine and increase the death rate. An improved protocol considering the persistent neuroinflammation induced by electrode implants will address refinement and reduction, two of the 3Rs principles for the ethical use of animals in scientific research.<\/jats:p>","DOI":"10.3390\/biom14070834","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T11:28:03Z","timestamp":1720783683000},"page":"834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Glial Response and Neuronal Modulation Induced by Epidural Electrode Implant in the Pilocarpine Mouse Model of Epilepsy"],"prefix":"10.3390","volume":"14","author":[{"given":"Giulia","family":"Spagnoli","sequence":"first","affiliation":[{"name":"Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0365-5144","authenticated-orcid":false,"given":"Edoardo","family":"Parrella","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy"},{"name":"Section of Innovation Biomedicine, Department of Engineering for Innovation Medicine, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7537-5871","authenticated-orcid":false,"given":"Sara","family":"Ghazanfar Tehrani","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mengoni","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Salari","sequence":"additional","affiliation":[{"name":"Section of Innovation Biomedicine, Department of Engineering for Innovation Medicine, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Nistreanu","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7678-6359","authenticated-orcid":false,"given":"Ilaria","family":"Scambi","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Sbarbati","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6031-5130","authenticated-orcid":false,"given":"Giuseppe","family":"Bertini","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9644-4399","authenticated-orcid":false,"given":"Paolo Francesco","family":"Fabene","sequence":"additional","affiliation":[{"name":"Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy"},{"name":"Section of Innovation Biomedicine, Department of Engineering for Innovation Medicine, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.neubiorev.2021.08.020","article-title":"The pilocarpine model of mesial temporal lobe epilepsy: Over one decade later, with more rodent species and new investigative approaches","volume":"130","author":"Biagini","year":"2021","journal-title":"Neurosci. 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