Kainic acid-induced dorsal and ventral hippocampal seizures in rats

Akaike, Koichi; Tanaka, Shigeya; Tojo, Hideshi; Fukumoto, Shin-ichiro; Imamura, Shinichi; Takigawa, Morikuni

doi:10.1016/s0006-8993(01)02252-1

Cited by 39 publications

(23 citation statements)

References 12 publications

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“…The transient, nonprogressive nature of the seizure phenotype observed here, however, suggests that a compensatory mechanism was activated to suppress SRSs (and epileptogenesis), as has been seen in neurons that have lost tonic GABA conductance through the genetic knock-out of extrasynaptic receptors (Brickley et al, 2001). Given that the dorsal CA1 is classically thought not to be as epileptogenic as the ventral hippocampus or amygdala, it remains possible in future experiments that an interneuron lesion in one of these other areas could cause the mice to have a progressive and permanent epilepsy (Racine et al, 1977; Gilbert et al, 1985; Akaike et al, 2001; Ekstrand et al, 2011; Scholl et al, 2013; Toyoda et al, 2013). …”

Section: Discussionmentioning

confidence: 99%

Targeted Interneuron Ablation in the Mouse Hippocampus Can Cause Spontaneous Recurrent Seizures

Spampanato

Dudek

2017

eNeuro

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The death of GABAergic interneurons has long been hypothesized to contribute to acquired epilepsy. These experiments tested the hypothesis that focal interneuron lesions cause acute seizures [i.e., status epilepticus (SE)] and/or chronic epilepsy [i.e., persistent spontaneous recurrent seizures (SRSs)]. To selectively ablate interneurons, Gad2-ires-Cre mice were injected unilaterally in the CA1 area of the dorsal hippocampus with an adeno-associated virus containing the diphtheria toxin receptor (DTR). Simultaneously, an electrode, connected to a miniature telemetry device, was positioned at the injection site for chronic recordings of local field potentials (LFPs). Two weeks after virus transfection, intraperitoneal injection of DT consistently caused focal, specific, and extensive ablation of interneurons. Long-term, continuous monitoring revealed that all mice with DT-induced interneuron lesions had SRSs. Seizures lasted tens of seconds and interseizure intervals were several hours (or days); therefore, these interneuron lesions did not induce SE. The SRSs occurred 3-5 d after DT treatment, which is the estimated time required for DT-induced cell death; therefore, induction of SRSs occurred without the latent period typical of acquired epilepsy. In five of six DT-treated mice, SRSs stopped within days, suggesting that the DT-induced interneuron lesions did not usually cause epilepsy. In one mouse, however, SRSs occurred for ≥34 d after interneuron ablation, similar to epilepsy after experimental SE. Sham control mice had no detectable seizures, confirming that the SRSs were due to ablation of interneurons. These data show that selective interneuron ablation consistently caused SRSs but not SE; and, at least under the conditions used here, interneuron lesions rarely led to persistent SRSs (i.e., epilepsy).

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Section: Discussionmentioning

confidence: 99%

Targeted Interneuron Ablation in the Mouse Hippocampus Can Cause Spontaneous Recurrent Seizures

Spampanato

Dudek

2017

eNeuro

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“…The molecular and cellular indicators of excitotoxicity in the slice model were also observed in the KA rat model. KA is well known to evoke seizure activity leading to neurodegeneration, particularly hippocampal pathology [14,33,58]. Treatments with AM6701 or AM6702 were associated with decreased seizure scores in KA rats, with AM6701 producing a greater suppression of seizures and excitotoxic progression compared to AM6702.…”

Section: Discussionmentioning

confidence: 99%

Equipotent Inhibition of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase – Dual Targets of the Endocannabinoid System to Protect against Seizure Pathology

et al. 2012

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Advances in the understanding of the endogenous cannabinoid system have led to several therapeutic indications for new classes of compounds that enhance cannabinergic responses. Endocannabinoid levels are elevated during pathogenic conditions, and inhibitors of endocannabinoid inactivation promote such on-demand responses. The endocannabinoids anandamide and 2-arachidonoyl glycerol have been implicated in protective signaling against excitotoxic episodes, including seizures. To better understand modulatory pathways that can exploit such responses, we used the new generation compound AM6701 that blocks both the anandamide-deactivating enzyme fatty acid amide hydrolase (FAAH) and the 2-arachidonoyl glycerol-deactivating enzyme monoacylglycerol lipase (MAGL) with equal potency. Also studied was the structural isomer AM6702 which is 44-fold more potent for inhibiting FAAH versus MAGL. When applied before and during kainic acid (KA) exposure to cultured hippocampal slices, AM6701 protected against the resulting excitotoxic events of calpain-mediated cytoskeletal damage, loss of presynaptic and postsynaptic proteins, and pyknotic changes in neurons. The equipotent inhibitor was more effective than its close relative AM6702 at protecting against the neurodegenerative cascade assessed in the slice model. In vivo, AM6701 was also the more effective compound for reducing the severity of KA-induced seizures and protecting against behavioral deficits linked to seizure damage. Corresponding with the behavioral improvements, cytoskeletal and synaptic protection was elicited by AM6701, as found in the KA-treated hippocampal slice model. It is proposed that the influence of AM6701 on FAAH and MAGL exerts a synergistic action on the endocannabinoid system, thereby promoting the protective nature of cannabinergic signaling to offset excitotoxic brain injury.

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“…Transitory limbic convulsions of stages 1-2 were observed during 2-4 h after injection. Later no convulsions were observed, this fact indicating that the convulsive activity was located in the limbic system and did not manifest after 48 h according to electrophysiological values [2]. Controls were injected with isotonic NaCl in the same volumes during the same periods as the experimental rats.…”

Section: Methodsmentioning

confidence: 98%

Expression of mGluR5 and Synaptophysin Genes after Injury to the Dorsal Hippocampus, Inflicted by Cainic Acid

Lebedev

Архипов

2009

Bull Exp Biol Med

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The expression of synaptophysin (vesicular protein) and mGluR5 (metabotropic glutamate receptor) genes was studied 3, 7, and 20 days after cainic acid injury of the dorsal hippocampal area in Wistar rats. The expression of both genes was characteristically reduced in the hippocampus. Twenty days after the exposure the expression of mGluR5 in this brain area reached the control level, while synaptophysin expression remained low. An opposite trend was observed in the frontal cortex: synaptophysin expression 20 days after exposure did not differ from the control, while mGluR5 expression was reduced. The peculiar time course of both genes' expression in the hippocampus and frontal cortex indicates the involvement of the frontal cortex in mechanisms of functional recovery after hippocampal injuries.

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Kainic acid-induced dorsal and ventral hippocampal seizures in rats

Cited by 39 publications

References 12 publications

Targeted Interneuron Ablation in the Mouse Hippocampus Can Cause Spontaneous Recurrent Seizures

Targeted Interneuron Ablation in the Mouse Hippocampus Can Cause Spontaneous Recurrent Seizures

Equipotent Inhibition of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase – Dual Targets of the Endocannabinoid System to Protect against Seizure Pathology

Expression of mGluR5 and Synaptophysin Genes after Injury to the Dorsal Hippocampus, Inflicted by Cainic Acid

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