SEARCH

SEARCH BY CITATION

Keywords:

  • neural stem cell;
  • gliogenesis;
  • epileptogenesis;
  • pilocarpine;
  • hippocampus

Abstract

Neurogenesis persists in the adult rat rostral forebrain subventricular zone (SVZ) and is stimulated by status epilepticus (SE). More caudal SVZ (cSVZ) neural progenitors migrate to the hippocampus after ischemic injury and contribute to CA1 pyramidal cell regeneration. Because SE also damages the hippocampus, we examined the effects of SE on cSVZ precursors. SE was induced in adult rats with pilocarpine, and cell proliferation in cSVZ and hippocampus was examined by bromodeoxyuridine (BrdU) and retroviral reporter labeling. Neural precursors were assayed by immunostaining for specfic markers between 1 and 35 days after SE. BrdU-positive cells labeled prior to SE markedly increased in numbers within 1–2 weeks in the cSVZ and infracallosal region, but not in the corpus callosum. Doublecortin-, polysialic acid neural cell adhesion molecule-, and TUC-4 (TOAD/Ulip/CRMP family-4)-immunostained cells with migrating morphology increased with a similar time course after SE and extended from the cSVZ to CA1 and CA3 regions. Retroviral reporters injected into the cSVZ of controls showed labeled cells with oligodendroglial morphology located in the cSVZ and corpus callosum; when injected 2 days prior to SE, many more reporter-labeled cells appeared several weeks later and were located in the cSVZ, corpus callosum, and hippocampus. Labeled cells showed glial morphologies and expressed astrocyte or oligodendrocyte markers. Neither BrdU- nor retroviral reporter-labeled cells coexpressed neuronal markers in controls or pilocarpine-treated rats. These results indicate that SE increases cSVZ gliogenesis and attracts newly generated glia to regions of hippocampal damage. Further study of seizure-induced gliogenesis may provide insight into mechanisms of adult neural progenitor regulation and epileptogenesis. © 2006 Wiley-Liss, Inc.