Kainic acid-induced seizures: Dose-relationship of behavioural neurochemical and histopathological changes

Sperk, Günther; Lassmann, Hans; Baran, Halina; Seitelberger, F; Hornykiewicz, Oleh

doi:10.1016/0006-8993(85)90159-3

Cited by 192 publications

(102 citation statements)

References 28 publications

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“…The pattern of damage induced by systemically administered kainate approximates to that seen following repeated temporal lobe seizures (Ben Ari, 1985) and cerebral ischemia-reperfusion (Dykens et al, 1987). Therefore, kainate provides a valuable tool with which to model some features of ischemic damage and of the injury induced by repeated epileptic seizures (Sperk et al, 1985).…”

Section: Introductionmentioning

confidence: 86%

“…The behavior of the animals was evaluated during 4 h after injection of kainate according to the following rating scale (Sperk et al, 1985): 0: normal, rare wet dog shakes, no convulsions; 1: intermediate number of wet dog shakes, rare focal convulsions affecting head and extremities, staring and intense immobility; 2: frequent wet dog shakes, frequent focal convulsions (no rearing or salivation); 3: frequent wet dog shakes, progression to more severe convulsions with rearing and salivation (but without falling over); 4: continuous generalized seizures (rearing, falling over), salivation; 5: generalized tonic-clonic seizures, death within 4 h in status epilepticus.…”

Section: Evaluation Of Behavioral Changesmentioning

confidence: 99%

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Nimesulide limits kainate-induced oxidative damage in the rat hippocampus

Candelario‐Jalil

Ajamieh

Sam

et al. 2000

European Journal of Pharmacology

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Kainate induces a marked expression of cyclooxygenase-2 after its systemic administration. Because cyclooxygenase-2 activity is associated to the production of reactive oxygen species, we investigated the effects of nimesulide, a selective cyclooxygenase-2 inhibitor, on kainateinduced in vivo oxidative damage in the rat hippocampus. A clinically relevant dose of nimesulide (6 mg/kg, i.p.) was administered 3 times following kainate application (9 mg/kg, i.p.). After 24 h of kainate administration, the drastic decrease in hippocampal glutathione content and the significant increase in lipid peroxidation were attenuated in nimesulide-treated rats, suggesting that the induction of cyclooxygenase-2 is involved in kainate-mediated free radicals formation.

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Section: Introductionmentioning

confidence: 86%

Section: Evaluation Of Behavioral Changesmentioning

confidence: 99%

Nimesulide limits kainate-induced oxidative damage in the rat hippocampus

Candelario‐Jalil

Ajamieh

Sam

et al. 2000

European Journal of Pharmacology

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“…Administration of KA is known to induce a sequence of altered behavioral events characterized by epileptiform seizures (Ben-Ari et al 1980, Sperk 1994, which are followed by neurodegeneration in specific brain regions, such as the hippocampus, piriform cortex, thalamus, and amygdala. In the hippocampus, the CA3 pyramidal cells and interneurons in the hilus of the dentate gyrus are the most vulnerable, followed by CA1 pyramidal cells (Coyle 1983, Sperk et al 1985, Tauck & Nadler 1985. Although the exact molecular mechanisms underlying excitotoxicity-induced cell death remain unclear, it has been shown that the activation of microglia and astrocytes in the hippocampus and consequent enhanced release of reactive oxygen species and proinflammatory cytokine may play an important role in KA-induced neurodegenerative processes (Wang et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Ghrelin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus

Lee¹,

Lim²,

Kim³

et al. 2010

Journal of Endocrinology

108

111

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Ghrelin is an endogenous ligand for GH secretagogue receptor type 1a (GHSR1a), and is produced and released mainly from the stomach. It has been recently demonstrated that ghrelin can function as a neuroprotective factor by inhibiting apoptotic pathways. Kainic acid (KA), an excitatory amino acid L-glutamate analog, causes neuronal death in the hippocampus; previous studies suggest that activated microglia and astrocytes actively participate in the pathogenesis of KA-induced hippocampal neurodegeneration. However, it is unclear whether ghrelin has neuroprotective effect in KA-induced hippocampal neurodegeneration. I.p. injection of KA produced typical neuronal cell death in the CA1 and CA3 pyramidal layers of the hippocampus, and the systemic administration of ghrelin significantly attenuated KA-induced neuronal cell death in these regions through the activation of GHSR1a. Ghrelin prevents KA-induced activation of microglia and astrocytes, and the expression of proinflammatory mediators tumor necrosis factor a, interleukin-1b, and cyclooxygenase-2. The inhibitory effect of ghrelin on the activation of microglia and astrocytes appears to be associated with the inhibition of matrix metalloproteinase-3 expression in damaged hippocampal neurons. Our data suggest that ghrelin has a therapeutic potential for suppressing KA-induced pathogenesis in the brain.

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“…Indeed, a strong body of evidence using models of seizure-induced epilepsy has documented that prolonged limbic seizures (status epilepticus) as well as kindling (Cavazos et al , 1994) result in hippocampal cell loss in a pattern reminiscent of that found in human temporal lobe epilepsy (e.g., Lothman and Collins, 1981 ;Nadler, 1981;Ben-Ari, 1985;Sperk et al, 1985;Obenaus et al, 1993;Buckmaster and Dudek, 1997). This cell loss has been found to be progressive (Sutula, 1991;Kalviainen et al, 1998), and associated with -in fact, probably required for (Schauwecker et al, 2000) -synaptic reorganization and increased excitability in the involved circuits (Dudek et al, 1994;Scharfman et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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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Kainic acid-induced seizures: Dose-relationship of behavioural neurochemical and histopathological changes

Cited by 192 publications

References 28 publications

Nimesulide limits kainate-induced oxidative damage in the rat hippocampus

Nimesulide limits kainate-induced oxidative damage in the rat hippocampus

Ghrelin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus

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

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