Prolonged infusion of cycloheximide does not block mossy fiber sprouting in a model of temporal lobe epilepsy

Epilepsia. 2005 Jul;46(7):1017-20. doi: 10.1111/j.1528-1167.2005.04605.x.


Purpose: The role of protein synthesis in mossy fiber sprouting is unclear. Conflicting reports exist on whether a single dose of the protein synthesis-blocker cycloheximide administered around the time of an epileptogenic injury can block the eventual development of mossy fiber sprouting.

Methods: In rats, osmotic minipumps and cannulae were implanted to deliver 8 mg/ml cycloheximide to one dentate gyrus and vehicle to the other. This method has been used to block protein synthesis in the infused region for up to 5 days with minimal neurotoxic effects (Taha and Stryker, Neuron 2002;34:425-36). After 2 days of infusion, rats were treated with pilocarpine to induce status epilepticus. Pumps were removed 3 days later. Thirty days after pilocarpine treatment, rats were perfused, and hippocampal sections were processed for Timm staining.

Results: Timm staining revealed aberrant mossy fiber sprouting in the inner molecular layer regardless of whether hippocampi were treated with cycloheximide or vehicle. Cycloheximide-treated hippocampi displayed more aberrant Timm staining and more tissue damage around the infusion site than did vehicle-treated hippocampi.

Conclusions: Prolonged infusion of cycloheximide, spanning the period of pilocarpine treatment, did not block mossy fiber sprouting. This finding suggests that protein-dependent mechanisms around the time of an epileptogenic injury are not necessary for the eventual development of synaptic reorganization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cycloheximide / pharmacology*
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / physiopathology
  • Disease Models, Animal
  • Epilepsy, Temporal Lobe / chemically induced*
  • Epilepsy, Temporal Lobe / physiopathology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Mossy Fibers, Hippocampal / drug effects*
  • Mossy Fibers, Hippocampal / physiopathology
  • Neuronal Plasticity
  • Pilocarpine
  • Protein Synthesis Inhibitors / pharmacology*
  • Rats
  • Status Epilepticus / chemically induced
  • Status Epilepticus / physiopathology
  • Synapses / drug effects
  • Synapses / physiology


  • Protein Synthesis Inhibitors
  • Pilocarpine
  • Cycloheximide