Caudal Subventricular Zone Neural Precursors Increase Proliferation and Form Ectopic Glia after Pilocarpine-Induced Status Epilepticus.
Abstract number :
2.015
Submission category :
Year :
2001
Submission ID :
1673
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
J.M. Parent, MD, Neurology, University of Michigan, Ann Arbor, MI; R. Liu, MD, Neurology, University of Michigan, Ann Arbor, MI; N. von dem Bussche, MD, Radiology, University of California, San Diego, San Diego, CA; D.H. Lowenstein, MD, Neurology, Beth Is
RATIONALE: Neural precursors continue to proliferate in the adult rodent forebrain subventricular zone (SVZ). We previously found that pilocarpine-induced status epilepticus (SE) increases neurogenesis in the rostral SVZ, a neurogenic region in the adult rat. By contrast, the caudal (c) SVZ is a putative gliogenic germinative zone. The aim of this study was to determine the effects of SE on proliferation, migration and differentiation of adult rat cSVZ precursors.
METHODS: Adult rats were given BrdU to label proliferating cells 1-2 d before, or 7 d after, the induction of SE for 2 h with systemic pilocarpine. Coronal sections through the cSVZ at dorsal hippocampal levels were immunostained for BrdU and neural precursor markers after 3-35 d. Additional animals received stereotaxic injections of retrovirus carrying green fluorescent protein or [beta]-gal reporters into the cSVZ 1 d prior to SE, and the locations and morphology of retrovirus labeled cells were identified 1-4 wks later. Controls received saline in place of pilocarpine.
RESULTS: BrdU labeling markedly increased 1-2 wks after SE in the cSVZ, infracallosal band, and hippocampal CA1 and CA3 regions but not in the corpus callosum. Immunostaining for the neural precursor markers doublecortin, the polysialylated form of neural cell adhesion molecule, and collapsin response mediator protein-4 also increased in these areas after SE. Immunolabeled cells had migrating cell morphology and incorporated BrdU, but did not co-express neuron-specific markers. Retroviral reporter-labeled cells in controls appeared exclusively in the cSVZ and corpus callosum. After seizures, many more cells expressed the retroviral reporters, not only in the cCSV and corpus callosum, but also in the hippocampus. All of the cells had astrocyte or oligodendrocyte morphology.
CONCLUSIONS: These data show that SE increases cSVZ gliogenesis, and that newly generated glia migrate to injured hippocampal regions. Further study of seizure-induced gliogenesis may provide insight into the regulation of glial precursor proliferation and migration, as well as into epileptogenic mechanisms.
Support: NINDS NS02006 (JMP) and NS35628, NS39950 (DHL)