Neurochemical Research

, Volume 42, Issue 10, pp 2730–2742 | Cite as

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

  • Adriana Fernanda K. VizueteEmail author
  • Matheus Mittmann Hennemann
  • Carlos Alberto Gonçalves
  • Diogo Losch de Oliveira
Original Paper


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.


Astrocyte dysfunction Astrogliosis Epilepsy Pilocarpine S100B 



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.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interests.

Supplementary material

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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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Adriana Fernanda K. Vizuete
    • 1
    Email author
  • Matheus Mittmann Hennemann
    • 1
  • Carlos Alberto Gonçalves
    • 1
  • Diogo Losch de Oliveira
    • 1
  1. 1.Department of Biochemistry, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil

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