Pyramidal cell responses to γ-aminobutyric acid differ in type I and Type II cortical dysplasia
Mental Retardation Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. Journal of Neuroscience Research
(Impact Factor: 2.59).
11/2008; 86(14):3151-62. DOI: 10.1002/jnr.21752
Abnormalities in the gamma-aminobutyric acid (GABA)-ergic system could be responsible for seizures in cortical dysplasia (CD). We examined responses of pyramidal neurons to exogenous application of GABA, as well as alterations of GABAergic interneuron number and size in pediatric epilepsy surgery patients with non-CD, type I CD, and type II CD pathologies. We used the dissociated cell preparation for electrophysiology along with immunohistochemistry to identify number and size of GABAergic cells. Pyramidal neurons from type I CD tissue showed increased EC(50) and faster kinetics compared with cells from non-CD and type II CD tissue. Cytomegalic pyramidal neurons showed increased GABA peak currents and decreased peak current densities, longer kinetics, and decreased sensitivity to zolpidem and zinc compared with normal pyramidal cells from non-CD and type I CD. There were fewer but larger glutamic acid decarboxylase (GAD)-containing cells in type II CD tissue with cytomegalic neurons compared with non-CD, type I CD, and type II CD without cytomegalic neurons. In addition, GABA transporters (VGAT and GAT-1) showed increased staining surrounding cytomegalic neurons in type II CD tissue. These results indicate that there are differences in GABA(A) receptor-mediated pyramidal cell responses in type I and type II CD. Alterations in zolpidem and zinc sensitivities also suggest that cytomegalic neurons have altered GABA(A) receptor subunit composition. These findings support the hypothesis that patients with type I and type II CD will respond differently to GABA-mediated antiepileptic drugs and that cytomegalic neurons have features similar to immature neurons with prolonged GABA(A) receptor open channel times.
Available from: Senthilvelan Manohar
- "The specificity of this antibody for parvalbumin in the rodent brain was described by Felch and Van Hooser (2012). It was also shown to label neurons in cortex of rat and mouse (Salgado et al., 2007; Schmid et al., 2008) and also used in a study of cortical dysplasia in humans (Andr e et al., 2008). "
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ABSTRACT: The dorsal cochlear nucleus (DCN) is a brainstem structure that receives input from the auditory nerve. Many studies in a diversity of species have shown that the DCN has a laminar organization and identifiable neuron types with predictable synaptic relations to each other. In contrast, studies on the human DCN have found a less distinct laminar organization and fewer cell types, although there has been disagreement among studies in how to characterize laminar organization and which of the cell types identified in other animals are also present in humans. We have reexamined DCN organization in the human using immunohistochemistry to analyze the expression of several proteins that have been useful in delineating the neurochemical organization of other brainstem structures in humans: nonphosphorylated neurofilament protein (NPNFP), nitric oxide synthase (nNOS), and three calcium-binding proteins. The results for humans suggest a laminar organization with only two layers, and the presence of large projection neurons that are enriched in NPNFP. We did not observe evidence in humans of the inhibitory interneurons that have been described in the cat and rodent DCN. To compare humans and other animals directly we used immunohistochemistry to examine the DCN in the macaque monkey, the cat, and three rodents. We found similarities between macaque monkey and human in the expression of NPNFP and nNOS, and unexpected differences among species in the patterns of expression of the calcium-binding proteins. Anat Rec, 2014. © 2014 Wiley Periodicals, Inc.
Available from: Lino Nobili
- "Furthermore, immunocytochemical (ICC) studies have revealed the peculiar aspect of the affected cortex suggesting that, in addition to the structural disarrangement, neurochemical organisation is also disrupted (Spreafico et al., 1998; Garbelli et al., 1999; Tassi et al., 2001). Recent electrophysiological studies performed on dissociated neurons and brain slices obtained from surgical specimens with proven type II FCD have also reported anomalous cellular behaviour (D'Antuono et al., 2004; Cepeda et al., 2007; Andre et al., 2008). These abnormal cytoarchitectural, neurochemical, and electrophysiological characteristics suggest selective morphofunctional alterations in type II FCD that might explain the distinctive ictal and interictal EEG patterns (Tassi et al., 2002; Garbelli et al., 1999; Chassoux et al., 2000). "
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ABSTRACT: Focal cortical dysplasias (FCDs) are highly epileptogenic malformations associated with drug-resistant epilepsy, susceptible to surgical treatment. Among the different types of FCD, the type II includes two subgroups based on the absence (IIa) or presence (IIb) of balloon cells. The aim of this retrospective study was to investigate possible differences in electroclinical presentations and surgical outcomes between the two subgroups in 100 consecutive surgically treated patients with type II FCDs. All patients underwent a comprehensive presurgical assessment including stereo-EEG (SEEG) when necessary. No significant differences in gender, age at epilepsy onset, duration of epilepsy, age at surgery or seizure frequency were found between the two subgroups. Patients with type IIb FCD frequently showed sleep-related epilepsy. Their peculiar electrographic pattern was characterised by localised rhythmic or pseudo-rhythmic spikes or polyspikes ("brushes") enhanced during non-REM sleep and also associated with well-localised, brief, low-voltage fast activity. The incidence and frequency of short bursts of fast discharges, interrupted by activity suppression, increased during slow-wave sleep and often recurred pseudo-periodically. The occurrence of "brushes", present in 76% of the patients with type IIb FCD, was significantly associated (p<0.001) with the presence of balloon cells. We discuss the possible pathogenetic mechanisms underlying this activity. MRI diagnosis of type II FCD was made in 93% of the patients with balloon cells (BCs), suggesting that the presence of balloon cells might be, at least partially, responsible for the MRI features. Patients had very good postsurgical outcomes (83% in Engel class I) even after a long period of follow-up.
Available from: Wim van Drongelen
- "viousstudiesofpediatricepileptictissue(Andreetal.,2004); however,wedidnotdirectlytestforthisinourstudy.Because burstingwasinducedalsointhepresenceofbicuculline,differences inGABAAreceptorsensitivity(Andreetal.,2008)orsubunit compositioncouldalsocontributetothisdifference(Jansenetal., 2008).Thisconclusionwouldbeconsistentwiththehypothesisthat abnormalitiesintheGABAergicandglutamatergic(NMDAreceptor )systemcouldcontributetotheseizuresinCD. "
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ABSTRACT: To test the hypothesis that focal and parafocal neocortical tissue from pediatric patients with intractable epilepsy exhibits cellular and synaptic differences, the authors characterized the propensity of these neurons to generate (a) voltage-dependent bursting and (b) synaptically driven paroxysmal depolarization shifts. Neocortical slices were prepared from tissue resected from patients with intractable epilepsy. Multiunit network activity and simultaneous whole-cell patch recordings were made from neurons from three patient groups: (1) those with normal histology; (2) those with mild and severe cortical dysplasia; and (3) those with abnormal pathology but without cortical dysplasia. Seizure-like activity was characterized by population bursting with concomitant bursting in intracellularly recorded cortical neurons (n = 59). The authors found significantly more N-methyl-D-aspartic acid-driven voltage-dependent bursting neurons in focal versus parafocal tissue in patients with severe cortical dysplasia (P < 0.01). Occurrence of paroxysmal depolarization shifts and burst amplitude and burst duration were significantly related to tissue type: focal or parafocal (P < 0.05). The authors show that functional differences between focal and parafocal tissue in patients with severe cortical dysplasia exist. There are functional differences between patient groups with different histology, and bursting properties can be significantly associated with the distinction between focal and parafocal tissue.
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