Early Aberrant Growth of Mossy Fibers after Status Epilepticus in the Immature Rat Brain

Abstract

Axonal sprouting is recognized to be an important mean of repair after neurologic injury. Some characteristic aftermaths of pilocarpine-induced status epilepticus (SE) in the immature rat are nerve cell loss and rearrangement of neuronal fibers. SE induced cell degeneration exclusively in the hippocampal CA1 subfield. Development of neuronal death becomes evident within hours after SE, following a delayed time course ranging from 6 to 48 h post-SE. An incidental finding is that pilocarpine induces within 48 h an aberrant growth of hippocampal mossy fibers in the hippocampus, especially in the infrapyramidal region of the CA3-subfield. We found a strong infrapyramidal band of mossy fibers along the entire stratum oriens of the CA3-region. No mossy fibers sprouting into the inner molecular layer of the dentate gyrus, or CA1 sprouting into the stratum moleculare of CA1 were noted. Signs of aberrant connectivity were found in six of the 10 pilocarpine-treated animals. This study provides the demonstration that pilocarpine within 48 h consistently results in the formation of ectopic hippocampal mossy fibers in a 2-week-old pup. This indicates a high degree of axonal reorganization in the hippocampus. It remains controversial whether such reorganization is the cause or consequence of chronic seizures. We assume that these additional infrapyramidal mossy fibers may influence the way in which granule cells drive pyramidal cells in CA3.

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Acknowledgements

We thank Professor J. Stehle for scientific support of our work. This work was supported partly by the Adolf-Messer-Stiftung (grant to A. Rami—“Molecular mechanisms of autophagy”).

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Rami, A., Niquet, J. & Konoplew, A. Early Aberrant Growth of Mossy Fibers after Status Epilepticus in the Immature Rat Brain. Mol Neurobiol 56, 5025–5031 (2019). https://doi.org/10.1007/s12035-018-1432-y

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Keywords

  • Status epilepticus
  • Pilocarpine
  • Hippocampus
  • Mossy fibers
  • Immature rat