Status Epilepticus Causes Necrotic Damage in the Mediodorsal Nucleus of the Thalamus in Immature Rats

Kubová, Hana; Druga, R; Łukasiuk, Katarzyna; Suchomelova, Lucie; Haugvicová, Renata; Jirmanová, Isa; Pitkänen, Asla

doi:10.1523/jneurosci.21-10-03593.2001

Cited by 157 publications

(114 citation statements)

References 41 publications

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“…A loss of neurons due to necrosis and apoptosis in the hippocampus has been reported in epilepsy (Kubova et al 2001;Zhang et al 1998). In addition, patients suffering from mesial temporal lobe epilepsy used in this study showed hippocampal sclerosis characterized by pyramidal neuron loss on pathological examination.…”

Section: Down-regulation Of Pimt In the Hippocampus Of Epileptic Patisupporting

confidence: 50%

Down‐regulation of protein l‐isoaspartyl methyltransferase in human epileptic hippocampus contributes to generation of damaged tubulin

Lanthier

Bouthillier

Lapointe

et al. 2002

Journal of Neurochemistry

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Protein L-isoaspartyl methyltransferase (PIMT) repairs the damaged proteins which have accumulated abnormal aspartyl residues during cell aging. Gene targeting has elucidated a physiological role for PIMT by showing that mice lacking PIMT died prematurely from fatal epileptic seizures. Here we investigated the role of PIMT in human mesial temporal lobe epilepsy. Using surgical specimens of hippocampus and neocortex from controls and epileptic patients, we showed that PIMT activity and expression were 50% lower in epileptic hippocampus than in controls but were unchanged in neocortex. Although the protein was down-regulated, PIMT mRNA expression was unchanged in epileptic hippocampus, suggesting post-translational regulation of the PIMT level. Moreover, several proteins with abnormal aspartyl residues accumulate in epileptic hippocampus. Microtubules component b-tubulin, one of the major PIMT substrates, had an increased amount (two-fold) of L-isoaspartyl residues in the epileptic hippocampus. These results demonstrate that the down-regulation of PIMT in epileptic hippocampus leads to a significant accumulation of damaged tubulin that could contribute to neuron dysfunction in human mesial temporal lobe epilepsy.

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Section: Down-regulation Of Pimt In the Hippocampus Of Epileptic Patisupporting

confidence: 50%

Down‐regulation of protein l‐isoaspartyl methyltransferase in human epileptic hippocampus contributes to generation of damaged tubulin

Lanthier

Bouthillier

Lapointe

et al. 2002

Journal of Neurochemistry

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“…Finally, in the immature brain, normal cell death occurs, and these dying cells may also be labeled. Because of the potential ambiguities of each of the methods described here regarding its specificity for cell death, a recent trend (Sankar et al, 1998;Toth et al, 1998;Kubova et al, 2001) has been the adoption of several methods in combination. In addition, several time points have often been analyzed in recent studies of seizure-induced neuronal death in the immature brain.…”

Section: Do Argyrophilia Acid-fuchsin Staining or In Situ End-labelimentioning

confidence: 99%

“…Sankar et al ( 1998) used several methods, including Fluoro-jade, to assess pilocarpine-induced cell death. In an elegant recent study, Kubova et al (2001) resorted to electron microscopy to determine categorically that seizures killed specific populations in discrete thalamic nuclei.…”

Section: Do Argyrophilia Acid-fuchsin Staining or In Situ End-labelimentioning

confidence: 99%

“…These experiments have attempted to provide clues about the immediate and long-term consequences of early-life seizures in the human, and in particular, about the relationship of seizures, such as those induced by neonatal asphyxia (Jensen et al, 1991), fever (Shinnar, 1998) or other triggers (Baram and Hatalski , 1998), to subsequent epilepsy. Specifically, whether seizures early in life cause cell death, and whether this death is required, sufficient, or even related, to subsequent epilepsy has been a topic of intense investigation (for discussions see Sperber et al, 1999;Dube et al, 2000;Kubova et al, 2001;Bender and Baram, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Is neuronal death required for seizure-induced epileptogenesis in the immature brain?

Baram

Eghbal-Ahmadi

Bender

2002

Progress in Brain Research

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Do seizures cause neuronal death? At least in the immature hippocampus, this may not be the critical question for determining the mechanisms of epileptogenesis. Neuronal injury and death have clearly been shown to occur in most epilepsy models in the mature brain, and are widely considered a prerequisite to seizure-induced epilepsy. In contrast, little neuronal death occurs after even a severe and prolonged seizure prior to the third postnatal week. However, seizures early in life, for example prolonged experimental febrile seizures, can profoundly and permanently change the hippocampal circuit in a pro-epileptogenic direction. These seizure-induced alterations of limbic excitability may require transient structural injury, but are mainly due to functional changes in expression of gene coding for specific receptors and channels, leading to altered functional properties of hippocampal neurons. Thus, in some pro-epileptogenic models in the developing brain, neither the death of neurons nor death-induced abnormalities of surviving neurons may underlie the formation of an epileptic circuit. Rather, findings in the experimental prolonged febrile seizure model suggest that persistent functional alterations of gene expression ('neuroplasticity') in diverse hippocampal neuronal populations may promote pro-epileptogenic processes induced by these seizures. These findings also suggest that during development, relatively short, intense bursts of neuronal activity may disrupt 'normal' programmed maturational processes to result in permanent, selective alterations of gene expression, with profound functional consequences. Therefore, determining the cascade of changes in the programmed expression of pertinent genes, including their temporal and cell-specific spatial profiles, may provide important information for understanding the process of transformation of an evolving, maturing hippocampal network into one which is hyperexcitable.

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“…Status epilepticus induced by lithium pilocarpine in immature rats causes neuronal damage in the MD, which appears to be necrosis rather than apoptosis. 11,12) Injection of kainic acid into the ventro-lateral nucleus of the thalamus (VL) caused generalized spike and wave complexes. 1) Excitation of the VL probably involved the mechanism of the spike and wave complexes, but the spike and wave complex was of very short duration at 20 seconds.…”

Section: Introductionmentioning

confidence: 99%

Experimental Petit Mal-Like Seizure Induced by Microinjection of Kainic Acid Into the Unilateral Mediodorsal Nucleus of the Thalamus

Kato

Urino

Hori

et al. 2008

Neurol. Med. Chir.(Tokyo)

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The mediodorsal nucleus (MD) of the thalamus has reciprocal projections with the frontal cortex and limbic system, and may be involved in absence seizures. Kainic acid was injected into the left MD of Wistar rats, and behavior and electroencephalography were monitored for 24 hours, then continued intermittently for 8 weeks. The rat brains were then examined histologically. Brain metabolic changes were also investigated by intravenous injection of 100 mCi/kg of [ 14 C]2-deoxyglucose to measure local cerebral glucose metabolism. Bilateral synchronous spike and wave complexes appeared almost 2 hours after kainic acid injection, and the waveforms continued for about 5-7 hours in the bilateral MDs, ipsilateral sensorimotor cortex, and basolateral nucleus of the amygdala. The associated behavioral changes were mainly those of behavioral arrest and staring, associated with occasional limbic seizures. Clear metabolic increases were found in the ipsilateral frontal cortex, hippocampus, and amygdala. The present results suggest that the MD was involved in both the mechanism of spike and wave complexes in the bilateral frontal cortices, and in seizure propagation to the limbic system. Consequently, kainic acid-induced MD seizure is associated with significant cognitive impairment and may explain the mechanism of petit mal seizure.

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Status Epilepticus Causes Necrotic Damage in the Mediodorsal Nucleus of the Thalamus in Immature Rats

Cited by 157 publications

References 41 publications

Down‐regulation of protein l‐isoaspartyl methyltransferase in human epileptic hippocampus contributes to generation of damaged tubulin

Down‐regulation of protein l‐isoaspartyl methyltransferase in human epileptic hippocampus contributes to generation of damaged tubulin

Is neuronal death required for seizure-induced epileptogenesis in the immature brain?

Experimental Petit Mal-Like Seizure Induced by Microinjection of Kainic Acid Into the Unilateral Mediodorsal Nucleus of the Thalamus

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