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Glial Response and Neuronal Modulation Induced by Epidural Electrode Implant in the Pilocarpine Mouse Model of Epilepsy

Authors :
Giulia Spagnoli
Edoardo Parrella
Sara Ghazanfar Tehrani
Francesca Mengoni
Valentina Salari
Cristina Nistreanu
Ilaria Scambi
Andrea Sbarbati
Giuseppe Bertini
Paolo Francesco Fabene
Source :
Biomolecules, Vol 14, Iss 7, p 834 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

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.

Details

Language :
English
ISSN :
2218273X
Volume :
14
Issue :
7
Database :
Directory of Open Access Journals
Journal :
Biomolecules
Publication Type :
Academic Journal
Accession number :
edsdoj.71c9d66184ad4774ac5c6de4ec5d28b8
Document Type :
article
Full Text :
https://doi.org/10.3390/biom14070834