Expression of AMPA receptor subunits in hippocampus after status convulsion

Hu, Yue; Jiang, Li; Chen, Hengsheng; Zhang, Xiaoping

doi:10.1007/s00381-012-1747-3

Cited by 19 publications

(13 citation statements)

References 27 publications

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“…In addition, pilocarpine has been shown to induce oxidative brain damage when administered systemically, but not intracerebroventricularly, even though a different dosage and localization of lateral ventricle with respect to the bregma was used compared with the present study [16]; therefore, we speculate that the wide diffuse distribution of the drug into the brain through the lateral ventricle may account for the distinct results observed. In addition to the fact that intracerebroventricular pilocarpine administration provides a good distribution of drug into the brain including the hippocampus, it has been shown that this region showed neurodegeneration, neuronal loss (by necrosis or apoptosis), and gliosis after the administration of pilocarpine in rats [20][21][22][23]; however, additional experiments are necessary to determine the spread of damage in the hippocampus by intracerebroventricular pilocarpine administration. In summary, we believe that this model of TLE, unlike the systemic model, is a good alternative for researching the mechanisms underlying the generation and maintenance of seizures, considering that the animals were injected with a single dose of .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of behavioral parameters and mortality in a model of temporal lobe epilepsy induced by intracerebroventricular pilocarpine administration

Medina‐Ceja

Pardo-Peña²,

Ventura-Mejía³

2014

NeuroReport

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The pilocarpine model of temporal lobe epilepsy (TLE) is a useful tool that is used to investigate the mechanisms underlying the generation and maintenance of seizures. Although this model has been modified significantly to reduce mortality and to promote the appearance of spontaneous recurrent seizures, to date, no detailed evaluation has been performed of the behavioral parameters and mortality in TLE induced by intracerebroventricular pilocarpine administration; therefore, this was the goal of the present study. A single dose of pilocarpine hydrochloride (2.4 mg in a total volume of 2 µl) was injected into the right lateral brain ventricle of rats; the convulsive behavior was rated using the Racine scale and the mortality was analyzed in these animals. We found that 30-90 min after animals received intracerebroventricular pilocarpine injections, 73% developed status epilepticus (SE) with an activity score of 4/5 on the Racine scale. Moreover, these seizures were associated with the propagation of epileptiform activity to different hippocampal regions. Of the animals that developed SE, spontaneous recurrent seizures were observed in 32.5% at different times after SE induction. A 35% mortality rate was observed, which included animals that died during pilocarpine injection and after SE induction. On the basis of these findings, and given the observed latency between the insult (SE induction by pilocarpine injection) and the manifestation of spontaneous recurrent seizures, we propose that this model is a useful tool for basic biomedical research of SE and TLE.

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Section: Discussionmentioning

confidence: 99%

Evaluation of behavioral parameters and mortality in a model of temporal lobe epilepsy induced by intracerebroventricular pilocarpine administration

Medina‐Ceja

Pardo-Peña²,

Ventura-Mejía³

2014

NeuroReport

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“…It is notable that most of these models also represent animal models of epileptogenesis; considering the aim of this review, we only include discussion of relevant changes within the first 24 hours after the initiation of SE, which might be considered relevant to this phenomenon, although some processes may also be linked to epileptogenesis . Some of these studies have underscored how changes in the expression of AMPARs could be subunit and brain‐region specific . However, these studies focused particularly on temporal lobe regions and above all on the hippocampus and piriform cortex, describing seemingly contradictory results with augmented, reduced, or unchanged AMPARs subunit expression.…”

Section: Ampa Receptors In Status Epilepticusmentioning

confidence: 99%

“…30 Moreover, GluA2-lacking AMPA receptors promote excitotoxicity and neurodegeneration by means of Ca 2+ entry in neurons that normally express Ca 2+ -impermeable channels contributing to, or causing, delayed cell death in response to endogenous glutamate. 21,31,32 Relevant plastic changes in the expression and functioning of AMPARs, and particularly in their subunit composition, have been demonstrated already during early stages of SE in several animal models including the lithium-pilocarpine, 33,34 pilocarpine-, 35 kainate-induced SE 36,37 (Table 1).…”

Section: Ampa Receptors In Status Epilepticusmentioning

confidence: 99%

“…38 Some of these studies have underscored how changes in the expression of AMPARs could be subunit and brainregion specific. 33,34 However, these studies focused particularly on temporal lobe regions and above all on the hippocampus and piriform cortex, describing seemingly contradictory results with augmented, reduced, or unchanged AMPARs subunit expression. Such variability could be due to the different experimental procedures used to induce SE as well as to the employment of different strain and/or ages of animals.…”

Section: Ampa Receptors In Status Epilepticusmentioning

confidence: 99%

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The role of AMPA receptors and their antagonists in status epilepticus

et al. 2018

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Status epilepticus (SE) is typically defined as a prolonged self-sustaining seizure or repeated seizures showing an incomplete recovery between them. SE represents a medical emergency often associated with significant disability, morbidity, and mortality. Despite the clinical impact, the mechanisms underlying the transition from self-limited seizures to protracted, medically refractory seizures are not completely understood. About 40% of patients in established SE are refractory to antiepileptic drugs (first-line treatment); therefore, there is a need for more efficacious drugs. In this review, we focused on the current knowledge about the involvement of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors during SE, the preclinical efficacy of its antagonists, and the currently published clinical studies involving drugs with this mechanism of action. We carried out an extensive literature search to recognize experimental and clinical articles both on AMPA receptors and AMPA antagonists and SE. Recently, the role of AMPA receptors during and after SE has become clearer, and it is now widely accepted that early changes occur in the initial stages and probably contribute both to the maintenance of SE and to its refractoriness to treatment. The therapeutic potential of AMPA receptor inhibition has been sustained by studies in which AMPA receptor antagonists have been shown to terminate seizures in several SE animal models. To date, promising, but limited, data in humans support the use of AMPA receptor antagonists in patients with SE. AMPA receptor antagonists could become a new therapeutic option in patients with established SE when the first trials with second-line agents have failed or probably even better after failure of benzodiazepines as a second-line option.

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“…This is determined by the permeability of the receptor to Ca 2+ ions, and is dependent on the expression of the GluA2 subunit which limits Ca 2+ permeability [248]. Epilepsy is common in ASD and FXS, and AMPARs are implicated in its pathophysiology and treatments [249, 250]. This is a broad topic that is a subject of a review on its own.…”

Section: Ampar Alterations In Animal Models Of Asd and Fxs And Inmentioning

confidence: 99%

The Role of Ionotropic Glutamate Receptors in Childhood Neurodevelopmental Disorders: Autism Spectrum Disorders and Fragile X Syndrome

Uzunova¹,

Hollander²,

Shepherd

2014

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Autism spectrum disorder (ASD) and Fragile X syndrome (FXS) are relatively common childhood neurodevelopmental disorders with increasing incidence in recent years. They are currently accepted as disorders of the synapse with alterations in different forms of synaptic communication and neuronal network connectivity. The major excitatory neurotransmitter system in brain, the glutamatergic system, is implicated in learning and memory, synaptic plasticity, neuronal development. While much attention is attributed to the role of metabotropic glutamate receptors in ASD and FXS, studies indicate that the ionotropic glutamate receptors (iGluRs) and their regulatory proteins are also altered in several brain regions. Role of iGluRs in the neurobiology of ASD and FXS is supported by a weight of evidence that ranges from human genetics to in vitro cultured neurons. In this review we will discuss clinical, molecular, cellular and functional changes in NMDA, AMPA and kainate receptors and the synaptic proteins that regulate them in the context of ASD and FXS. We will also discuss the significance for the development of translational biomarkers and treatments for the core symptoms of ASD and FXS.

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Expression of AMPA receptor subunits in hippocampus after status convulsion

Abstract: Immature brain was more resistant to seizure-induced neural damage. The time course of reduction and recovery differed for each subunit and was dependent on developmental stage. The increased expression of GluR2 could confer early but transient protection in the immature brain after SC.

Cited by 19 publications

References 27 publications

Evaluation of behavioral parameters and mortality in a model of temporal lobe epilepsy induced by intracerebroventricular pilocarpine administration

Evaluation of behavioral parameters and mortality in a model of temporal lobe epilepsy induced by intracerebroventricular pilocarpine administration

The role of AMPA receptors and their antagonists in status epilepticus

The Role of Ionotropic Glutamate Receptors in Childhood Neurodevelopmental Disorders: Autism Spectrum Disorders and Fragile X Syndrome

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