The NMDA receptor NR2B subunit contributes to epileptogenesis in human cortical dysplasia

Möddel, Gabriel; Jacobson, Benjamin; Zhang, Ying; Janigro, Damir; Bingaman, William; González-Martínez, Jorge; Kellinghaus, Christoph; Prayson, Richard A.; Najm, Imad

doi:10.1016/j.brainres.2005.03.042

Cited by 91 publications

(53 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Different results were reported about seizure effects on NR2B expression: tissue from patients with drug-resistant epilepsy has shown a differentially increased expression of NR2B and a contribution of this subunit to epileptogenesis in human cortical dysplasia has been suggested [14]. In the pentylenetetrazol-induced kindling seizure, no significant alteration of NR2B expression appeared in cortex and hippocampus [15], kindling does not produce long-lasting changes in NMDAR subunits expression in hippocampus [16].…”

Section: Introductionmentioning

confidence: 95%

The NMDAR Subunit NR2B Expression is Modified in Hippocampus after Repetitive Seizures

2008

View full text Add to dashboard Cite

NMDA receptor is involved in synaptic plasticity, learning, memory and neurological diseases like epilepsia and it is the major mediator of excitotoxicity. NR2B-containing NMDA receptors may be playing a crucial role in epileptic disorders. In the present study the effect of the convulsant drug 3-mercaptopropionic acid (MP) repetitive administration (4-7 days) on the hippocampal NR2B subunit was studied. A significant decrease in NR2B in the whole hippocampus was observed after MP4 with a tendency to recover to normal values in MP7 by western blot assay. Immunohistochemical studies showed a decrease in several CA1 and CA2/3 strata (21-73%). MP7 showed a reversion of the drop observed at 4 days in stratum oriens, pyramidal cell layer in CA1, CA2/3 and CA1 stratum radiatum. A significant fall in the lacunosum molecular layer of both areas and stratum radiatum of CA2/3 was observed. The immunostaining in MP4 showed a decrease in the granulare layer from dentate gyrus (20%), in hillus (71%) and subicullum (63%) as compared with control and these decreases were similar at MP7 values. Results showed decreases in NR2B subunit expression in different areas following repeated MP-induce seizures, suggesting that NR2B expression is altered depending on the diverse hippocampal input and output signals of each region that could be differently involved in modulating MP-induced hyperactivity.

show abstract

Section: Introductionmentioning

confidence: 95%

The NMDAR Subunit NR2B Expression is Modified in Hippocampus after Repetitive Seizures

2008

View full text Add to dashboard Cite

show abstract

“…There is some evidence to suggest that balloon cells display intrinsic hyperexcitability, possibly because of a modification of N-methyl-d-aspartate receptors or decreased sensitivity of the γ-aminobutyric acid A receptors in these pacemaker cells. 10,18,19,31,32 In more diffuse cortical dysplasia, there may be abnormal connectivity of the cellular aggregate, which is associated with reorganization of cortical circuitry, and axons that would normally project out of the epileptic zone may also be interrupted and instead make excitatory synapses locally. These recurrent excitatory connections may cause feed-forward connectivity loops that drive the excitatory and consequent epileptic process.…”

Section: Volumetrics and Epileptogenesismentioning

confidence: 99%

The influence of lesion volume, perilesion resection volume, and completeness of resection on seizure outcome after resective epilepsy surgery for cortical dysplasia in children

Oluigbo¹,

Wang²,

Whitehead

et al. 2015

PED

View full text Add to dashboard Cite

OBJECT Focal cortical dysplasia (FCD) is one of the most common causes of intractable epilepsy leading to surgery in children. The predictors of seizure freedom after surgical management for FCD are still unclear. The objective of this study was to perform a volumetric analysis of factors shown on the preresection and postresection brain MRI scans of patients who had undergone resective epilepsy surgery for cortical dysplasia and to determine the influence of these factors on seizure outcome. METHODS The authors reviewed the medical records and brain images of 43 consecutive patients with focal MRI-documented abnormalities and a pathological diagnosis of FCD who had undergone surgical treatment for refractory epilepsy. Preoperative lesion volume and postoperative resection volume were calculated by manual segmentation using OsiriX PRO software. RESULTS Forty-three patients underwent first-time surgery for resection of an FCD. The age range of these patients at the time of surgery ranged from 2 months to 21.8 years (mean age 7.3 years). The median duration of follow-up was 20 months. The mean age at onset was 31.6 months (range 1 day to 168 months). Complete resection of the area of an FCD, as adjudged from the postoperative brain MR images, was significantly associated with seizure control (p = 0.0005). The odds of having good seizure control among those who underwent complete resection were about 6 times higher than those among the patients who did not undergo complete resection. Seizure control was not significantly associated with lesion volume (p = 0.46) or perilesion resection volume (p = 0.86). CONCLUSIONS The completeness of FCD resection in children is a significant predictor of seizure freedom. Neither lesion volume nor the further resection of perilesional tissue is predictive of seizure freedom.

show abstract

“…Among the iGluRs, the role of N-methyl-Daspartate (NMDA) receptors (GluN) in cortical hyperexcitability has received considerable attention. Several studies have shown alteration in GluN subunit expression in human epileptic tissue with increased expression of the subunit NR2B [149][150][151][152]. Changes in the expression of components of the membrane-associated guanylate kinase (MAGUK) protein family, interacting with GluN, has been also reported [153,154].…”

Section: Epileptogenesismentioning

confidence: 99%

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

Aronica

Crino

2014

Neurotherapeutics

View full text Add to dashboard Cite

show abstract

The NMDA receptor NR2B subunit contributes to epileptogenesis in human cortical dysplasia

Cited by 91 publications

References 50 publications

The NMDAR Subunit NR2B Expression is Modified in Hippocampus after Repetitive Seizures

The NMDAR Subunit NR2B Expression is Modified in Hippocampus after Repetitive Seizures

The influence of lesion volume, perilesion resection volume, and completeness of resection on seizure outcome after resective epilepsy surgery for cortical dysplasia in children

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

Contact Info

Product

Resources

About