Effects of early-life LiCl-pilocarpine-induced status epilepticus on memory and anxiety in adult rats are associated with mossy fiber sprouting and elevated CSF S100B protein

Epilepsia. 2008 May;49(5):842-52. doi: 10.1111/j.1528-1167.2007.01484.x. Epub 2008 Jan 2.

Abstract

Purpose: This study investigated putative correlations among behavioral changes and: (1) neuronal loss, (2) hippocampal mossy fiber sprouting, and (3) reactive astrogliosis in adult rats submitted to early-life LiCl-pilocarpine-induced status epilepticus (SE).

Methods: Rats (P15) received LiCl (3 mEq/kg, i.p.) 12-18 h prior pilocarpine (60 mg/kg; s.c.). At adulthood, animals were submitted to behavioral tasks and after the completion of tasks biochemical and histological analysis were performed.

Results: In SE group, it was observed an increased number of degenerating neurons in the CA1 subfield and in the hilus of animals 24 h after SE. At adulthood, SE group presented an aversive memory deficit in an inhibitory avoidance task and the animals that presented lower latency to the step down showed a higher score for mossy fiber sprouting. In the light-dark exploration task, SE rats returned less and spent less time in the light compartment and present an increased number of risk assessment behavior (RA). There was a negative correlation between the time spent in the light compartment and the score for mossy fiber sprouting and a positive correlation between score for mossy fiber sprouting and number of RA. LiCl-pilocarpine-treated animals showed higher levels of S100B immunocontent in the CSF as well as a positive correlation between the score for sprouting and the GFAP immunocontent in the CA1 subfield, suggesting an astrocytic response to neuronal injury.

Conclusions: We showed that LiCl-pilocarpine-induced SE during development produced long-lasting behavioral abnormalities, which might be associated with mossy fiber sprouting and elevated CSF S100B levels at adulthood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn / growth & development
  • Anxiety / chemically induced
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Fear / drug effects
  • Fear / psychology
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Lithium Chloride / pharmacology
  • Memory / drug effects
  • Memory / physiology
  • Mossy Fibers, Hippocampal / drug effects
  • Mossy Fibers, Hippocampal / physiopathology
  • Nerve Growth Factors / blood
  • Pilocarpine / pharmacology
  • Rats
  • Rats, Wistar
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins / blood
  • Status Epilepticus / blood
  • Status Epilepticus / chemically induced*
  • Status Epilepticus / physiopathology

Substances

  • Nerve Growth Factors
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins
  • S100b protein, rat
  • Pilocarpine
  • Lithium Chloride