title: Neuronal degeneration is observed in multiple regions outside the hippocampus after lithium pilocarpine-induced status epilepticus in the immature rat.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, United States.
authors.forename: E A
authors.initials: EA
authors.lastname: Scholl
authors.forename: F E
authors.initials: FE
authors.lastname: Dudek
authors.forename: J J
authors.initials: JJ
authors.lastname: Ekstrand
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology*; D008094:Lithium / Q000633:toxicity; D009410:Nerve Degeneration / Q000473:pathology*; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology*
chemical_list: D003292:Convulsants; D010862:Pilocarpine; D008094:Lithium
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
references.citation: Brain Res. 2001 Sep 21;913(2):117-32
references.pmid: 11549375
references.citation: J Comp Neurol. 2005 Mar 21;483(4):476-88
references.pmid: 15700275
references.citation: Epilepsy Res. 1996 Dec;26(1):115-21
references.pmid: 8985693
references.citation: Ann Neurol. 1993 Jun;33(6):622-31
references.pmid: 8498843
references.citation: J Neurosci. 1998 Oct 15;18(20):8382-93
references.pmid: 9763481
references.citation: Epilepsy Res. 1993 Dec;16(3):223-33
references.pmid: 8119273
references.citation: J Neurosurg. 1992 Aug;77(2):185-93
references.pmid: 1625005
references.citation: Epilepsy Curr. 2011 Jan;11(1):21-6
references.pmid: 21461261
references.citation: Brain. 2011 Oct;134(Pt 10):2800-1
references.pmid: 21921018
references.citation: Brain Res. 1987 Dec 15;465(1-2):43-58
references.pmid: 3440212
references.citation: Epilepsy Res. 1998 Sep;32(1-2):233-53
references.pmid: 9761324
references.citation: Epilepsia. 2005;46 Suppl 5:38-42
references.pmid: 15987251
references.citation: Neuroscience. 2011 Sep 29;192:699-707
references.pmid: 21669257
references.citation: Ann Neurol. 1989 May;25(5):423-31
references.pmid: 2673001
references.citation: Epilepsy Res. 1997 Sep;28(2):129-36
references.pmid: 9267777
references.citation: J Cereb Blood Flow Metab. 1999 Feb;19(2):195-209
references.pmid: 10027775
references.citation: Neurosurgery. 1995 Nov;37(5):982-90; discussion 990-1
references.pmid: 8559349
references.citation: Epilepsia. 1991 Nov-Dec;32(6):778-82
references.pmid: 1743148
references.citation: Brain Res. 1995 Oct 30;697(1-2):197-204
references.pmid: 8593577
references.citation: Neuroscience. 2011 Aug 25;189:316-29
references.pmid: 21616128
references.citation: Epilepsy Curr. 2010 Jul;10(4):95-9
references.pmid: 20697505
references.citation: Epilepsia. 2002 Apr;43(4):325-35
references.pmid: 11952761
references.citation: J Comp Neurol. 2003 Dec 1;467(1):60-79
references.pmid: 14574680
references.citation: J Comp Neurol. 1997 Sep 1;385(3):385-404
references.pmid: 9300766
references.citation: Hippocampus. 2001;11(4):452-68
references.pmid: 11530850
references.citation: Epilepsy Res. 1996 Dec;26(1):207-18
references.pmid: 8985701
references.citation: Neuroscience. 2003;118(3):667-80
references.pmid: 12710975
references.citation: J Neurophysiol. 1998 Dec;80(6):2836-47
references.pmid: 9862888
references.citation: Br Med J. 1956 Dec 15;2(5006):1403-7
references.pmid: 13374345
references.citation: Can J Neurol Sci. 1991 Nov;18(4 Suppl):603-5
references.pmid: 1777879
references.citation: Epilepsia. 1993 Nov-Dec;34(6):985-95
references.pmid: 7694849
references.citation: Brain Res. 1997 Mar 14;751(1):37-46
references.pmid: 9098566
references.citation: Epilepsia. 2001 Aug;42(8):967-78
references.pmid: 11554881
references.citation: J Neurosci. 2003 Sep 17;23(24):8471-9
references.pmid: 13679415
references.citation: Eur J Neurosci. 2004 Jul;20(2):403-18
references.pmid: 15233750
references.citation: Neuroscience. 1999;94(2):473-95
references.pmid: 10579210
references.citation: Trends Neurosci. 1997 Nov;20(11):517-23
references.pmid: 9364666
references.citation: J Neurol Neurosurg Psychiatry. 1994 Sep;57(9):1099-105
references.pmid: 8089678
references.citation: Exp Neurol. 2005 May;193(1):125-30
references.pmid: 15817271
references.citation: J Neurosci. 2001 May 15;21(10):3593-9
references.pmid: 11331388
references.citation: Epilepsy Res. 1998 Sep;32(1-2):194-205
references.pmid: 9761320
references.citation: Curr Opin Neurol. 2012 Apr;25(2):194-200
references.pmid: 22322414
references.citation: Epileptic Disord. 2002 Jun;4(2):83-97
references.pmid: 12105072
references.citation: Neuroscience. 2009 Sep 29;163(1):415-29
references.pmid: 19540312
references.citation: Epilepsia. 1994 Jul-Aug;35(4):721-7
references.pmid: 8082614
references.citation: Nat Neurosci. 2001 Jan;4(1):52-62
references.pmid: 11135645
references.citation: Brain Res. 1976 Feb 27;103(3):527-34
references.pmid: 766914
references.citation: Ann Neurol. 2003 Apr;53(4):503-11
references.pmid: 12666118
references.citation: J Neurosci. 1993 Oct;13(10):4470-85
references.pmid: 8410199
references.citation: Neuroscience. 1994 Nov;63(1):7-18
references.pmid: 7898662
references.citation: Epilepsy Behav. 2009 Jan;14 Suppl 1:32-7
references.pmid: 18848643
references.citation: Toxicol Sci. 2004 Oct;81(2):364-70
references.pmid: 15254342
references.citation: Eur J Neurosci. 1996 Dec;8(12):2711-25
references.pmid: 8996821
references.citation: Brain Res. 1992 Jun 26;583(1-2):120-6
references.pmid: 1324090
references.citation: Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281-94
references.pmid: 4110397
references.citation: Epilepsia. 2002 Mar;43(3):219-27
references.pmid: 11906505
references.citation: Exp Neurol. 2001 Feb;167(2):227-41
references.pmid: 11161611
references.citation: Exp Neurol. 2004 Jun;187(2):367-79
references.pmid: 15144863
references.citation: Neuroscience. 1987 Dec;23(3):953-68
references.pmid: 3437996
references.citation: Acta Neurol Scand Suppl. 1988;117:52-60
references.pmid: 3176897
references.citation: Brain Res. 1996 Jun 24;725(1):11-22
references.pmid: 8828581
references.citation: J Comp Neurol. 2003 May 12;459(4):407-25
references.pmid: 12687707
references.citation: Brain. 1966 Sep;89(3):499-530
references.pmid: 5922048
references.citation: Arch Neurol. 1964 Mar;10:233-48
references.pmid: 14106980
references.citation: Neuropharmacology. 2011 Jul-Aug;61(1-2):313-28
references.pmid: 21539848
references.citation: Epilepsia. 2006 Mar;47(3):479-88
references.pmid: 16529609
references.citation: Epilepsia. 2002;43 Suppl 5:54-60
references.pmid: 12121296
references.citation: Brain Res. 2000 Aug 25;874(2):123-30
references.pmid: 10960596
references.citation: Epilepsy Behav. 2005 Dec;7 Suppl 3:S18-24
references.pmid: 16242383
references.citation: Epilepsia. 2003 Jul;44(7):893-903
references.pmid: 12823571
references.citation: Epilepsia. 2000;41 Suppl 6:S3-8
references.pmid: 10999511
references.citation: Behav Brain Res. 1983 Sep;9(3):315-35
references.pmid: 6639740
references.citation: Prog Brain Res. 2002;135:67-83
references.pmid: 12143371
references.citation: Epilepsia. 2004 Jun;45(6):695-714
references.pmid: 15144438
references.citation: Epilepsy Behav. 2008 Jul;13(1):62-9
references.pmid: 18337179
references.citation: Epilepsia. 2005;46 Suppl 5:31-7
references.pmid: 15987250
references.citation: Neurosurgery. 1984 Nov;15(5):667-71
references.pmid: 6504282
references.citation: Brain Res. 2001 Oct 26;917(1):45-54
references.pmid: 11602228