Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model

Borges, Karin, Gearing, Marla, McDermott, Dayna L., Smith, Amy B., Almonte, Antoine G., Wainer, Bruce H. and Dingledine, Raymond (2003) Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model. Experimental Neurology, 182 1: 21-34. doi:10.1016/S0014-4886(03)00086-4

Author Borges, Karin
Gearing, Marla
McDermott, Dayna L.
Smith, Amy B.
Almonte, Antoine G.
Wainer, Bruce H.
Dingledine, Raymond
Title Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model
Journal name Experimental Neurology   Check publisher's open access policy
ISSN 0014-4886
Publication date 2003-07-01
Year available 2003
Sub-type Article (original research)
DOI 10.1016/S0014-4886(03)00086-4
Open Access Status
Volume 182
Issue 1
Start page 21
End page 34
Total pages 14
Place of publication New York
Publisher Academic Press
Language eng
Subject 0601 Biochemistry and Cell Biology
11 Medical and Health Sciences
1101 Medical Biochemistry and Metabolomics
Abstract The rodent pilocarpine model of epilepsy exhibits hippocampal sclerosis and spontaneous seizures and thus resembles human temporal lobe epilepsy. Use of the many available mouse mutants to study this epilepsy model would benefit from a detailed neuropathology study. To identify new features of epileptogenesis, we characterized glial and neuronal pathologies after pilocarpine-induced status epilepticus (SE) in CF1 and C57BL/6 mice focusing on the hippocampus. All CF1 mice showed spontaneous seizures by 17–27 days after SE. By 6 h there was virtually complete loss of hilar neurons, but the extent of pyramidal cell death varied considerably among mice. In the mossy fiber pathway, neuropeptide Y (NPY) was persistently upregulated beginning 1 day after SE; NPY immunoreactivity in the supragranular layer after 31 days indicated mossy fiber sprouting. β2 microglobulin-positive activated microglia, normally absent in brains without SE, became abundant over 3–31 days in regions of neuronal loss, including the hippocampus and the amygdala. Astrogliosis developed after 10 days in damaged areas. Amyloid precursor protein immunoreactivity in the thalamus at 10 days suggested delayed axonal degeneration. The mortality after pilocarpine injection was very high in C57BL/6 mice from Jackson Laboratories but not those from Charles River, suggesting that mutant mice in the C57BL/6(JAX) strain will be difficult to study in the pilocarpine model, although their neuropathology was similar to CF1 mice. Major neuropathological changes not previously studied in the rodent pilocarpine model include widespread microglial activation, delayed thalamic axonal death, and persistent NPY upregulation in mossy fibers, together revealing extensive and persistent glial as well as neuronal pathology.
Keyword Epilepsy
Neuropeptide Y
Axonal degeneration
β2 Microglobulin
Amyloid precursor protein
Axonal degeneration
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID NS17771
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
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