Neuronal degeneration is observed in multiple regions outside the hippocampus after lithium pilocarpine-induced status epilepticus in the immature rat

Neuroscience. 2013 Nov 12:252:45-59. doi: 10.1016/j.neuroscience.2013.07.045. Epub 2013 Jul 27.


Although hippocampal sclerosis is frequently identified as a possible epileptic focus in patients with temporal lobe epilepsy, neuronal loss has also been observed in additional structures, including areas outside the temporal lobe. The claim from several researchers using animal models of acquired epilepsy that the immature brain can develop epilepsy without evidence of hippocampal neuronal death raises the possibility that neuronal death in some of these other regions may also be important for epileptogenesis. The present study used the lithium pilocarpine model of acquired epilepsy in immature animals to assess which structures outside the hippocampus are injured acutely after status epilepticus. Sprague-Dawley rat pups were implanted with surface EEG electrodes, and status epilepticus was induced at 20 days of age with lithium pilocarpine. After 72 h, brain tissue from 12 animals was examined with Fluoro-Jade B, a histochemical marker for degenerating neurons. All animals that had confirmed status epilepticus demonstrated Fluoro-Jade B staining in areas outside the hippocampus. The most prominent staining was seen in the thalamus (mediodorsal, paratenial, reuniens, and ventral lateral geniculate nuclei), amygdala (ventral lateral, posteromedial, and basomedial nuclei), ventral premammillary nuclei of hypothalamus, and paralimbic cortices (perirhinal, entorhinal, and piriform) as well as parasubiculum and dorsal endopiriform nuclei. These results demonstrate that lithium pilocarpine-induced status epilepticus in the immature rat brain consistently results in neuronal injury in several distinct areas outside of the hippocampus. Many of these regions are similar to areas damaged in patients with temporal lobe epilepsy, thus suggesting a possible role in epileptogenesis.

Keywords: AA; ACH; ACo; AD; AHC; AI; AM; AO; APir; AStr; AV; Acb; AcbSh; BAOT; BLA; BLP; BLV; BMA; BMP; BSTIA; BSTM; CA; CL; CM; CPu; CeL; CeM; Cg1-3; DEn; DG; DI; DLG; DP; EEG; Ent; Fluoro-jade B; Fr1-3; GABA; GI; GP; HC; Hil; I; IL; LDDM; LDVL; LHb; LM; LO; LOT; LPLR; LPMR; LSD; LSI; LSV; LaD; LaV; MD; MGD; MGM; MGP; MGV; MHb; MO; MS; MTu; MeA; MePD; MePV; NAc; Oc2L; P; PC; PF; PLCo; PMCo; PMD; PMV; PRh; PT; PVA; PVP; PaS; Par1; Pir; Po; PrS; RSA; RSG; Re; Rh; Rt; S; SG; SI; SNR; STh; TLE; Te1,3; VL; VLG; VLO; VM; VP; VPL; VPM; VTR; ZI; accumbens; accumbens shell; agranular insular cortex; amygdalopiriform transition area; amygdalostriatal transition area; anterior amygdaloid area; anterior cingulate; anterior cortical nucleus; anterior hypothalamic area; anterior hypothalamic area, central; anterior olfactory nucleus; anterodorsal nucleus; anteromedial; anteroventral nucleus; basolateral nucleus, anterior; basolateral nucleus, posterior; basolateral nucleus, ventral; basomedial nucleus, anterior; basomedial nucleus, posterior; bed nucleus accessory olfactory tract; bed nucleus stria terminalis, intraamygdaloid division; bed stria terminalis nuclei; caudate putamen; central nucleus, lateral; central nucleus, medial; centrolateral nucleus; centromedial nucleus; cornu ammonis; dentate gyrus; dorsal endopiriform nucleus; dorsal peduncular; dorsolateral geniculate nucleus; dysgranular insular cortex; electroencephalogram; entorhinal cortex; frontal cortex; globus pallidus; granular insular cortex; hilus; hippocampus; immature brain; infralimbic; intercalated masses; lateral habenula; lateral mammillary; lateral nucleus, dorsal; lateral nucleus, ventral; lateral orbital cortex; lateral septal, dorsal; lateral septal, intermediate; lateral septal, ventral; laterodorsal nucleus, dorsomedial; laterodorsal nucleus, ventrolateral; lateroposterior nucleus, lateral rostral; lateroposterior nucleus, medial rostral; lithium pilocarpine; medial geniculate nucleus, dorsal; medial geniculate nucleus, medial; medial geniculate nucleus, ventral; medial globus pallidus; medial habenula; medial nucleus, anterior; medial nucleus, posterodorsal; medial nucleus, posteroventral; medial orbital cortex; medial septal; medial tuberal; mediodorsal nucleus; nucleus accumbens; nucleus lateral olfactory tract; occipital cortex; paracentral; parafasicular; parasubiculum; paratenial; paraventricular nucleus, anterior; paraventricular nucleus, posterior; parietal cortex; perirhinal cortex; piriform cortex; post-natal day; posterior nucleus; posterolateral cortical nucleus; posteromedial cortical nucleus; premammillary nucleus, dorsal; premammillary nucleus, ventral; presubiculum; reticular nucleus; retrosplenial agranular cortex; retrosplenial granular cortex; reuniens nucleus; rhomboid nucleus; status epilepticus; subiculum; substantia innominate; substantia nigra pars reticulate; subthalamic nucleus; suprageniculate nucleus; temporal cortex; temporal lobe epilepsy; vRe; ventral pallidum; ventral posterolateral nucleus; ventral posteromedial nucleus; ventral reuniens nucleus; ventral tegmental area; ventrolateral geniculate nucleus; ventrolateral nucleus; ventrolateral orbital cortex; ventromedial nucleus; zona incerta; γ-aminobutyric acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain / pathology*
  • Convulsants / toxicity
  • Disease Models, Animal
  • Hippocampus / pathology*
  • Lithium / toxicity
  • Nerve Degeneration / pathology*
  • Pilocarpine / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Status Epilepticus / chemically induced
  • Status Epilepticus / pathology*


  • Convulsants
  • Pilocarpine
  • Lithium