Prolonged seizures recruit caudal subventricular zone glial progenitors into the injured 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.

Localized delivery of fibroblast growth factor–2 and brain-derived neurotrophic factor reduces spontaneous seizures in an epilepsy model

“…S5). In keeping with previous reports (6,18,20), this increase was observed in the dentate gyrus and in the pyramidal gyrus (especially CA1 strata oriens and lacunosum-molecularis, near the SVZ). Inoculation of the control vector did not alter this pattern.…”

“…In the adult hippocampus, neural progenitors are found both in the subgranular zone (SGZ) and in the caudal subventricular zone (SVZ). SE has been reported to increase proliferation of hippocampal progenitors in both areas, but SGZ progenitors differentiate into neurons that, in large part, migrate ectopically to the hilus and SVZ progenitors differentiate into glial, not neuronal, cells: that is, SE-induced neurogenesis is aberrant and may contribute to epileptogenesis (19,20).…”

Proliferation Changes in Dentate Gyrus of Hippocampus during the First Week following Kainic Acid-induced Seizures

“…This neuroplastic change is analogous to human and primate TLE and rodent models of TLE, where granule cell layer dispersion and hilar ectopic granule cells are prominent features of the epileptic hippocampus. 11,12) These new-born granule cells have been shown to be integrated into granule cell circuitry functionally and develop protective eŠect in epileptic activity, 12,13) but in this research its speciˆc signiˆcance still needs further elucidation.…”

Origin of Oligodendrocytes in the Subventricular Zone of the Adult Brain

“…Adult neural stem cells grown from the adult SVZ as neurospheres can generate oligodendrocytes (Morshead et al, 1994;Gritti et al, 1996;Weiss et al, 1996;Doetsch et al, 1999;Pluchino et al, 2003). Importantly, adult SVZ progenitors generate new oligodendrocytes in vivo after demyelinating lesions of the corpus callosum (CC) (Nait-Oumesmar et al, 1999;Picard-Riera et al, 2002) or after seizures (Parent et al, 2006). The primary progenitors for new oligodendrocytes born in the adult SVZ have not been identified.…”