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Protective effects of mossy fiber lesions against kainic acid-induced seizures and neuronal degeneration.

Publication ,  Journal Article
Okazaki, MM; Nadler, JV
Published in: Neuroscience
September 1988

The effects of a hippocampal mossy fiber lesion have been determined on neuronal degeneration and limbic seizures provoked by the subsequent intracerebroventricular administration of kainic acid to unanesthetized rats. Mossy fiber lesions were made either by transecting this pathway unilaterally or by destroying the dentate granule cells unilaterally or bilaterally with colchicine. All control rats eventually developed status epilepticus and each temporally discrete seizure that preceded status epilepticus was recorded from the hippocampus ipsilateral to the kainic acid infusion before the contralateral hippocampus. A mossy fiber lesion of the ipsilateral hippocampus prevented the development of status epilepticus in 26% of subjects and in 52% of subjects seizures were recorded from the contralateral hippocampus before the ipsilateral hippocampus. Unlike electrographic records from other treatment groups, those from rats which had received a bilateral colchicine lesion exhibited no consistent pattern indicative of seizure propagation from one limbic region to another. A bilateral, but not a unilateral, mossy fiber lesion also dramatically attenuated the behavioral expression of the seizures. Regardless of its effects on kainic acid-induced electrographic and behavioral seizures, a mossy fiber lesion always substantially reduced or completely prevented the degeneration of ipsilateral hippocampal CA3-CA4 neurons. This protective effect was specific for those hippocampal neurons deprived of mossy fiber innervation. Neurons in other regions of the brain were protected from degeneration only when the mossy fiber lesion also prevented the development of electrographic status epilepticus. These results suggest that the hippocampal mossy fibers constitute an important, though probably not an obligatory, link in the circuit responsible for the spread of kainic acid seizures. Degeneration of CA3-CA4 neurons appears to depend upon (1) the duration of hippocampal seizure activity and (2) an as yet undefined influence of or interaction with the mossy fiber projection which enhances the neurodegenerative effect of the seizures.

Duke Scholars

Published In

Neuroscience

DOI

ISSN

0306-4522

Publication Date

September 1988

Volume

26

Issue

3

Start / End Page

763 / 781

Location

United States

Related Subject Headings

  • Seizures
  • Reaction Time
  • Rats, Inbred Strains
  • Rats
  • Neurology & Neurosurgery
  • Nerve Degeneration
  • Male
  • Kainic Acid
  • Injections, Intraventricular
  • Hippocampus
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Okazaki, M. M., & Nadler, J. V. (1988). Protective effects of mossy fiber lesions against kainic acid-induced seizures and neuronal degeneration. Neuroscience, 26(3), 763–781. https://doi.org/10.1016/0306-4522(88)90097-8
Okazaki, M. M., and J. V. Nadler. “Protective effects of mossy fiber lesions against kainic acid-induced seizures and neuronal degeneration.Neuroscience 26, no. 3 (September 1988): 763–81. https://doi.org/10.1016/0306-4522(88)90097-8.
Okazaki, M. M., and J. V. Nadler. “Protective effects of mossy fiber lesions against kainic acid-induced seizures and neuronal degeneration.Neuroscience, vol. 26, no. 3, Sept. 1988, pp. 763–81. Pubmed, doi:10.1016/0306-4522(88)90097-8.
Journal cover image

Published In

Neuroscience

DOI

ISSN

0306-4522

Publication Date

September 1988

Volume

26

Issue

3

Start / End Page

763 / 781

Location

United States

Related Subject Headings

  • Seizures
  • Reaction Time
  • Rats, Inbred Strains
  • Rats
  • Neurology & Neurosurgery
  • Nerve Degeneration
  • Male
  • Kainic Acid
  • Injections, Intraventricular
  • Hippocampus