Status Epilepticus Increases Cell Proliferation and Neurogenesis in the Developing Rat Cerebellum

Cerebellum. 2020 Feb;19(1):48-57. doi: 10.1007/s12311-019-01078-6.

Abstract

Status epilepticus (SE) promotes neuronal proliferation and differentiation in the adult and developing rodent hippocampus. However, the effect of SE on other neurogenic brain regions such as the cerebellum has been less explored. To determine whether SE induced by pentylentetrazole (PTZ-SE) and lithium-pilocarpine (Li-Pilo-SE) increases cell proliferation and neurogenesis in the developing rat cerebellum. SE was induced in 14-day-old (P14) Wistar rat pups (both sexes). One hour after SE and the following day rats were injected intraperitoneally with 5-bromo-2'-deoxyuridine (BrdU, 50 mg/kg). Seven days after SE, immunohistochemistry was performed to detect BrdU-positive (BrdU+) cells or BrdU/NeuN+ cells in the cerebellar vermis. SE induced by PTZ or Li-Pilo statistically significant increased the number of cerebellar BrdU+ cells when compared with the control group (58% and 40%, respectively); maximal cell proliferation occurred in lobules II, III, VIb, VIc, VIII, IXa, and IXb of PTZ-SE group and II, V, VIc, VII, and X of Li-Pilo-SE group. An increased number of BrdU/NeuN+ cells was detected in lobules V (17 ± 1.9), VIc (25.8 ± 2.7), and VII (26.2 ± 3.4) after Li-Pilo-SE compared to their control group (9.8 ± 1.7, 12.8 ± 2.8, and 11 ± 1.7, respectively), while the number of BrdU/NeuN+ cells remained the same after PTZ-induced SE or control conditions. SE induced in the developing rat by different experimental models increases cell proliferation in the granular layer of the cerebellar vermis, but only SE of limbic seizures increases neurogenesis in specific cerebellar lobes.

Keywords: Cell proliferation; Immature brain; Lithium-Pilocarpine; Neurogenesis; Pentylenetetrazol; Status epilepticus.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology*
  • Cerebellum / drug effects
  • Cerebellum / growth & development*
  • Cerebellum / pathology*
  • Female
  • Lithium Chloride / toxicity
  • Male
  • Neurogenesis / drug effects
  • Neurogenesis / physiology*
  • Pentylenetetrazole / toxicity
  • Pilocarpine / toxicity
  • Rats
  • Rats, Wistar
  • Status Epilepticus / chemically induced*
  • Status Epilepticus / pathology*

Substances

  • Pilocarpine
  • Lithium Chloride
  • Pentylenetetrazole