Article

Immature Neurons and GABA Networks May Contribute to Epileptogenesis in Pediatric Cortical Dysplasia

Mental Retardation Research Center, David Geffen School of Medicine, University of California, Los Angeles, California 90024, USA.
Epilepsia (Impact Factor: 4.58). 02/2007; 48 Suppl 5(s5):79-85. DOI: 10.1111/j.1528-1167.2007.01293.x
Source: PubMed

ABSTRACT Cortical dysplasia (CD), a frequent pathological substrate of pediatric epilepsy surgery patients, has a number of similarities with immature cortex, such as reduced Mg2+ sensitivity of N-methyl-D-aspartate (NMDA) receptors and the persistence of subplate-like neurons and undifferentiated cells. Because gamma-aminobutyric acid (GABA) is the main neurotransmitter in early cortical development, we hypothesized increased GABA receptor-mediated synaptic function in CD tissue. Infrared videomicroscopy and whole-cell patch clamp recordings were used to characterize the morphology and electrophysiological properties of immature and normal-appearing neurons in slices from cortical tissue samples resected for the treatment of pharmacoresistant epilepsy in children (0.2-14 years). In addition, we examined spontaneous and evoked synaptic activity, as well as responses to exogenous GABA application. We demonstrate both the presence of immature pyramidal neurons and networks in young CD tissue and the predominance of GABA synaptic activity. In addition, spontaneous GABA depolarizations frequently induced action potentials, supporting a potential excitatory role of GABA in CD. Evoked synaptic responses mediated by GABA were also prominent, and bath application of 4-aminopyridine induced rhythmic depolarizations that were blocked by bicuculline. Finally, responses to exogenous application of GABA had depolarized reversal potentials in severe compared to mild and non-CD cases. The present data support the hypothesis that CD shares features of immature cortex, with predominant and potentially excitatory GABA(A) receptor-mediated neurotransmission. These results could partially explain the increased excitability of the cortical network in pediatric CD.

0 Followers
 · 
100 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Complex migraine aura in teenagers can be complicated to diagnose. The aim of this study was to present detailed features of migraine aura in teenage migraineurs. This cross-sectional study was conducted in the period from 2008 till 2013. A total number of 40 teenage migraineurs (20 females and 20 males) met criteria for this study. The patients were interviewed using a specially designed questionnaire for collecting data about migraine aura features. Main outcome measures were frequency of visual, somatosensory and higher cortical dysfunction (HCD) symptoms in teenage migraineurs population during the aura, and also within each individual. Visual aura was reported in every attack, followed by somatosensory (60%) and dysphasic (36.4%) aura. Scintillating scotoma and blurry vision were mostly reported and predominant visual symptoms. The most common somatosensory symptom was numbness in hand. HCD were reported by 22 (55%) patients. Slowed speech was mostly reported symptom of HCD, followed by dyslexia, deja vu phenomenon, color dysgnosia, and dyspraxia. In patients with HCD, aura frequency per year (6.18 +/- 3.17 vs. 3.33 +/- 2.03, p = 0.003) and prevalence of somatosensory symptoms (77.3% vs. 38.9%, p = 0.014) were significantly higher than in patients without HCD. Aura symptoms vary to a great extent in complexity in teenage migraineurs. Consequently, results obtained in this study provide useful information for clinicians when faced with unusual migraine aura.
    The Journal of Headache and Pain 12/2014; 15(1):87. DOI:10.1186/1129-2377-15-87 · 3.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human hypothalamic hamartoma (HH) is a rare developmental malformation often characterized by gelastic seizures, which are refractory to medical therapy. Ictal EEG recordings from the HH have demonstrated that the epileptic source of gelastic seizures lies within the HH lesion itself. Recent advances in surgical techniques targeting HH have led to dramatic improvements in seizure control, which further supports the hypothesis that gelastic seizures originate within the HH. However, the basic cellular and molecular mechanisms of epileptogenesis in this subcortical lesion are poorly understood. Since 2003, Barrow Neurological Institute has maintained a multidisciplinary clinical program to evaluate and treat patients with HH. This program has provided a unique opportunity to investigate the basic mechanisms of epileptogenesis using surgically resected HH tissue. The first report on the electrophysiological properties of HH neurons was published in 2005. Since then, ongoing research has provided additional insights into the mechanisms by which HH generate seizure activity. In this review, we summarize this progress and propose a cellular model that suggests that GABA-mediated excitation contributes to epileptogenesis in HH lesions.
    CNS Neuroscience & Therapeutics 12/2014; 21(2). DOI:10.1111/cns.12348 · 3.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epilepsy is a paroxysmal condition characterized by repeated transient seizures separated by longer interictal periods. Ictogenesis describes the processes of transition from the interictal state to a seizure. The processes include a preictal state, with specific clinical signs and a distinct electrophysiology which may provide opportunities to anticipate, or even prevent, seizures. Biological mechanisms of ictogenesis remain poorly understood and may vary between conditions/syndromes. We review here ictogenic processes including the involvement of pyramidal cells, interneurons and astrocytes, GABAergic and glutamatergic signaling, and ionic perturbations. Our review suggests that specific excitatory influences at the transition to an ictal event include (1) GABA receptor activation with a neuronal Cl(-) load and (2) a transient increase in external K(+).
    International Review of Neurobiology 01/2014; 114C:155-185. DOI:10.1016/B978-0-12-418693-4.00007-8 · 2.46 Impact Factor

Full-text (2 Sources)

Download
9 Downloads
Available from
Oct 13, 2014