Brain Repair in Temporal Lobe Epilepsy: An in Vivo Investigation
Abstract number :
1.098
Submission category :
2. Translational Research / 2B. Devices, Technologies, Stem Cells
Year :
2022
Submission ID :
2204299
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:24 AM
Authors :
Giulia Curia, PhD – University of Modena and Reggio Emilia; Stefania Bartoletti, MS – PhD student, Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia; Elisa Ren, PhD – Post-doc fellow, Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia; Beatrice Casadei Garofani, MS – Research Assistant, Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia; Alessandra Campanelli, MS – PhD student, Diagnostics and Public Health, University of Verona; Francesca Ciarpella, PhD – Post-doc fellow, Diagnostics and Public Health, University of Verona; Arianna Capodiferro, BS – MS student, Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia; Giuseppina Leo, PhD – Technician, Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia; Sissi Dolci, PhD – Technician, Diagnostics and Public Health, University of Verona; Gemma Palazzolo, PhD – Researcher, Italian Institute of Technology; Ilaria Decimo, PhD – Associate Professor, Diagnostics and Public Health, University of Modena and Reggio Emilia
Rationale: Temporal lobe epilepsy (TLE) is an adulthood focal epilepsy often refractory to anti-epileptic medications, and mesial TLE (MTLE) is its most severe form mainly characterized by hippocampal sclerosis. Intracerebral transplantation of neural stem cells (NSCs) is evolving as an attractive therapy for promoting regeneration and repair in various brain disorders, including TLE. Hostile environment, however, makes difficult NSC survival. In this regard, polymer carriers for cell delivery have been proposed as a promising approach to promote NSC survival, differentiation and maturation. Our aim was to characterize NSC survival and development in a hostile condition upon injection with or without the algal polysaccharide alginate.
Methods: Adult male Sprague Dawley rats were treated with pilocarpine to induce status epilepticus (SE), a brain insult leading to TLE. Three weeks later, rats were bilaterally injected with the cytotoxic agent ibotenic acid in ventral CA3 area, and 4 days later underwent NSC infusion with or without alginate. We assessed cell survival and cell maturation by a double immunofluorescence staining procedure performed 9 weeks after infusion. All experiments were in compliance with the European Directive 2010/63/EU and carried out according to the national guidelines on animal experimental research of the Italian Ministry of Health. All efforts were made to refine procedures to improve the welfare and to reduce the number of animals that were used.
Results: Most of the cells were positive for the stemness markers Sox2 and Vimentin, while only few cells expressed the immature neuron marker DCX. No cells were positive for the neuronal marker NeuN, while very few cells were positive for the specific marker of the intermediate filament proteins, Neurofilament M. Overall our data suggest that a small fraction of the transplanted cells differentiated into mature neurons, regardless the presence of alginate.
Conclusions: NSCs and alginate after 2-4-9 weeks are properly located in the injection site. NSCs at 2 weeks after transplantation are vital and tightly gathered in the injection site. NSCs at 9 weeks after transplantation show positivity for neuronal markers suggesting an ongoing maturation.
Funding: The present work was supported by European Union’s Horizon 2020 FETPROACT project HERMES (GA n. 824164).
Translational Research