Kainic Acid‐Induced Seizures and Brain Damage in the Rat: Different Effects of NMDA‐ and AMPA Receptor Antagonists

Berg, M.; Bruhn, Thomas; Diemer, Nils Henrik

doi:10.1111/j.1600-0773.1993.tb00582.x

Cited by 56 publications

(26 citation statements)

References 33 publications

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“…6,8 In the present study, treatment with MK-801 prevents kainateinduced NF-kB activation and neuronal death in CA1 of the hamster. Kainate binding sites are localized primarily in the CA3 and dentate gyrus in the hippocampal formation, 33,41 and treatment with kainate induces Ca 2ϩ entry in CA1 possibly via enhanced excitatory neurotransmission.…”

Section: Discussionmentioning

confidence: 47%

“…12,24 In support of this, NMDA antagonists as well as AMPA/kainate antagonists were reported to attenuate kainate-induced neuronal death and seizure activity. 6,8,9,11,22 Several studies suggest that kainate neurotoxicity may be mediated through down-regulation of glutamate receptor subunit 2 expression in the degenerating hippocampal areas, 14,32 which is expected to enhance Ca 2ϩ permeability through non-NMDA receptors and trigger neuronal death. In addition to ionotropic glutamate receptors, release and translocation of zinc may play a key role in triggering neuronal death following kainate administration.…”

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confidence: 99%

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Nuclear factor kappa B-mediated kainate neurotoxicity in the rat and hamster hippocampus

Won

Kim

et al. 1999

Neuroscience

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Section: Discussionmentioning

confidence: 47%

mentioning

confidence: 99%

Nuclear factor kappa B-mediated kainate neurotoxicity in the rat and hamster hippocampus

Won

Kim

et al. 1999

Neuroscience

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“…Electrophysiological studies show that estradiol treatment increases sensitivity of CA1 pyramidal cells to NMDA, but not non-NMDA receptor-mediated synaptic input (19), as well as prolongs excitatory postsynaptic potentials and increases repetitive firing in these cells (36). Because the development of KA-induced seizures involves NMDA-receptor activity (37,38), it is possible that enhanced NMDA-receptor function contributes to estrogen's facilatatory effect on KA-induced seizures.…”

Section: Effects Of Estradiol On Hippocampal Circuitrymentioning

confidence: 99%

Estradiol Facilitates Kainic Acid—Induced, but not Flurothyl‐Induced, Behavioral Seizure Activity in Adult Female Rats

Woolley

2000

Epilepsia

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Summary:Purpose: This study was designed to determine whether previously demonstrated increases in hippocampal axospinous synapse density and NMDA receptor function induced by estradiol are paralleled by increased susceptibility to limbic (kainic acid induced) or generalized (flurothyl induced) behavioral seizures.Methods: Kainic acid was injected systemically to ovariectomized adult female rats treated with either estradiol or oil vehicle. The latencies to each of five stages of seizure-related behaviors (staring, wet-dog shakes, head waving and chewing, forelimb clonus, rearing, and falling) were recorded for each animal. Flurothyl was administered by inhalation to ovariectomized adult female rats treated with estradiol alone, estradiol followed by short-term progesterone, or oil vehicle. The latencies to each of three stages of seizure-related behaviors (first myoclonic jerk, forelimb clonus, wild running and bouncing) were recorded for each animal.Results: Estradiol treatment decreased the latency to seizurerelated behaviors induced by kainic acid, but neither estradiol alone nor estradiol followed by progesterone had any effect on flurothyl-induced seizure-related behaviors. Conclusions:The same estradiol treatment paradigm known to induce structural and functional changes in the excitatory circuitry of the hippocampus facilitates the progression of kainic acid-induced seizures, which are known to involve the hippocampus, but has no effect on flurothyl-induced seizures. The lack of an effect of estradiol alone or estradiol followed by progesterone on flurothyl-induced seizures indicates that estradiol's effects on seizure susceptibility do not result from increased neuronal excitability throughout the brain, but rather involve action within the limbic system. The data suggest that structural and functional changes in hippocampal circuitry induced by estradiol may contribute to increased susceptibility to limbic seizure activity. Key Words: Catamenial epilepsyLimbic seizures-Hippocampus-CAI pyramidal cellsDendritic spines.Numerous clinical and experimental studies have demonstrated that estrogen can be proconvulsant. Clinically, an association between seizure frequency and the menstrual cycle in women with epilepsy (termed catamenial epilepsy) has been recognized for over 100 years (1). Although the prevalence of catamenial epilepsy has been controversial, many studies have documented a significant relationship between seizure occurrence and menses (reviewed in 2, 3). For example, a study of 184 women with intractable partial complex seizures reported that approximately one third exhibited at least a doubling of average daily seizure frequency during one of three phases of the menstrual cycle: perimenstrual, Accepted December 20, 1999. Address correspondence and reprint requests to Dr. C. S. Woolley at Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, U.S.A. E-mail: cwoolley@nwu.edu preovulatory, or second half of cycles with an inadequate luteal phase ( 3 ) . Each of th...

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“…Excessive production of oxygen-free radicals and other radical species often has been proposed to play an important role in neuronal pathology resulting from excitotoxic insults (3)(4)(5)(6)(7)(8). It generally is admitted that KA administration results in the activation of N-methyl-D-aspartate (NMDA) receptors in vulnerable neuronal populations (9,10), an event that has been shown to cause the formation of superoxide radicals (11,12). Moreover, we reported previously that levels of lipid peroxidation and protein oxidation, two parameters of oxidative stress, were increased significantly in hippocampus and piriform cortex at 8 and 16 h after KAinduced seizure activity in adult rats (13).…”

mentioning

confidence: 99%

EUK-134, a synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology

Rong

Doctrow

Tocco

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

254

187

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The present study tested the effects of EUK-134, a synthetic superoxide dismutase͞catalase mimetic, on several indices of oxidative stress and neuropathology produced in the rat limbic system as a result of seizure activity elicited by systemic kainic acid (KA) administration. Pretreatment of rats with EUK-134 did not modify the latency for or duration of KA-induced seizure activity. It did produce a highly significant reduction in increased protein nitration, activator protein-1-and NF-B-binding activity, and spectrin proteolysis as well as in neuronal damage resulting from seizure activity in limbic structures. These results support the hypothesis that kainate-induced excitotoxicity is caused, at least in part, by the action of reactive oxygen species. Furthermore, they suggest that synthetic superoxide dismutase͞catalase mimetics such as EUK-134 might be used to prevent excitotoxic neuronal injury.Various mechanisms have been proposed to account for the pathological manifestations observed after systemic administration of the excitotoxin kainic acid (KA). Because drugs blocking seizure activity prevent most of the neuronal damage resulting from KA injection (1, 2), it is clear that the pathology is not a direct consequence of the activation of KA or ␣-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptors, but rather is the result of events triggered by seizure activity. Excessive production of oxygen-free radicals and other radical species often has been proposed to play an important role in neuronal pathology resulting from excitotoxic insults (3-8). It generally is admitted that KA administration results in the activation of N-methyl-D-aspartate (NMDA) receptors in vulnerable neuronal populations (9, 10), an event that has been shown to cause the formation of superoxide radicals (11,12). Moreover, we reported previously that levels of lipid peroxidation and protein oxidation, two parameters of oxidative stress, were increased significantly in hippocampus and piriform cortex at 8 and 16 h after KAinduced seizure activity in adult rats (13). We also showed that the DNA-binding activity of two transcription factors, namely activator protein-1 (AP-1) and NF-B, generally considered to be markers of cellular insults (14, 15), was increased in these structures under these conditions (16). However, a causal relationship between oxidative stress and neuronal damage after systemic kainate injection has not been established unambiguously, because many agents used as antioxidants also interfere with seizure activity. In addition, because excitotoxicity also has been shown to be reduced by caspase inhibitors (17), oxidative stress could be a late consequence of the events triggered by seizure activity and leading to neuronal death.Salen-manganese complexes are low-molecular-weight synthetic compounds that exhibit both superoxide dismutase (SOD) and catalase activities, catalytically eliminating both superoxide and hydrogen peroxide, respectively (18 -20). Compared with proteinaceous antioxidant en...

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Kainic Acid‐Induced Seizures and Brain Damage in the Rat: Different Effects of NMDA‐ and AMPA Receptor Antagonists

Cited by 56 publications

References 33 publications

Nuclear factor kappa B-mediated kainate neurotoxicity in the rat and hamster hippocampus

Nuclear factor kappa B-mediated kainate neurotoxicity in the rat and hamster hippocampus

Estradiol Facilitates Kainic Acid—Induced, but not Flurothyl‐Induced, Behavioral Seizure Activity in Adult Female Rats

EUK-134, a synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology

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