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Phase-Dependent Astroglial Alterations in Li–Pilocarpine-Induced Status Epilepticus in Young Rats

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Abstract

Epilepsy prevalence is high in infancy and in the elderly population. Lithium–pilocarpine is widely used to induce experimental animal models of epilepsy, leading to similar neurochemical and morphological alterations to those observed in temporal lobe epilepsy. As astrocytes have been implicated in epileptic disorders, we hypothesized that specific astroglial changes accompany and contribute to epileptogenesis. Herein, we evaluated time-dependent astroglial alterations in the hippocampus of young (27-day-old) rats at 1, 14 and 56 days after Li–pilocarpine-induced status epilepticus (SE), corresponding to different phases in this model of epilepsy. We determined specific markers of astroglial activation: GFAP, S100B, glutamine synthetase (GS), glutathione (GSH) content, aquaporin-4 (AQP-4) and potassium channel Kir 4.1; as well as epileptic behavioral, inflammatory and neurodegenerative changes. Phase-dependent signs of hippocampal astrogliosis were observed, as demonstrated by increments in GFAP, S100B and GS. Astrocyte dysfunction in the hippocampus was characterized, based on the decrease in GSH content, AQP-4 and Kir 4.1 channels. Degenerating neurons were identified by Fluoro-Jade C staining. We found a clear, early (at SE1) and persistent (at SE56) increase in cerebrospinal fluid (CSF) S100B levels. Additionally, serum S100B was found to decrease soon after SE induction, implicating a rapid-onset increase in the CSF/serum S100B ratio. However, serum S100B increased at SE14, possibly reflecting astroglial activation and/or long-term increase in cerebrovascular permeability. Moreover, we suggest that peripheral S100B levels may represent a useful marker for SE in young rats and for follow up during the chronic phases of this model of epilepsy. Together, results reinforce and extend the idea of astroglial involvement in epileptic disorders.

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Acknowledgements

This study was supported by the National Council for Scientific and Technological Development (CNPq, Brazil), Ministry of Education (MEC/CAPES, Brazil), State Foundation for Scientific Research of Rio Grande do Sul (FAPERGS), National Institute of Science and Technology for Excitotoxicity and Neuroprotection (MCT/INCTEN), and project CNPq 27/2014-Neurodegenerative diseases.

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  1. Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil

    Adriana Fernanda K. Vizuete, Matheus Mittmann Hennemann, Carlos Alberto Gonçalves & Diogo Losch de Oliveira

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  1. Adriana Fernanda K. Vizuete
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Videomonitoring of SE animals between 1 and 8 weeks after pilocarpine injection. Animal development scores of 2 or 3, Racine scale. (MPG 90304 KB)

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Vizuete, A.F.K., Hennemann, M.M., Gonçalves, C.A. et al. Phase-Dependent Astroglial Alterations in Li–Pilocarpine-Induced Status Epilepticus in Young Rats. Neurochem Res 42, 2730–2742 (2017). https://doi.org/10.1007/s11064-017-2276-y

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