Glial Response and Neuronal Modulation Induced by Epidural Electrode Implant in the Pilocarpine Mouse Model of Epilepsy
Giulia Spagnoli,
Edoardo Parrella,
Sara Ghazanfar Tehrani,
Francesca Mengoni,
Valentina Salari,
Cristina Nistreanu,
Ilaria Scambi,
Andrea Sbarbati,
Giuseppe Bertini,
Paolo Francesco Fabene
Affiliations
Giulia Spagnoli
Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy
Edoardo Parrella
Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy
Sara Ghazanfar Tehrani
Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy
Francesca Mengoni
Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy
Valentina Salari
Section of Innovation Biomedicine, Department of Engineering for Innovation Medicine, University of Verona, 37134 Verona, Italy
Cristina Nistreanu
Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy
Ilaria Scambi
Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy
Andrea Sbarbati
Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy
Giuseppe Bertini
Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy
Paolo Francesco Fabene
Section of Anatomy and Histology, Department of Neurosciences, Biomedicine, and Movement Science, School of Medicine, University of Verona, 37124 Verona, Italy
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.
