ArticleAnnals of neurology2012
Altered inhibition in tuberous sclerosis and type IIb cortical dysplasia.
Article in Annals of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 180 citations in OpenAlex.
- Molecular Signature in Focal Cortical Dysplasia: A Systematic Review of RNA and Protein Data.International journal of molecular sciences · 2025Pooled it
- Effects of bumetanide on neurodevelopmental impairments in patients with tuberous sclerosis complex: an open-label pilot study.Molecular autism · 2020Trial
- Abnormal KCC2 expression and function in a mouse model of epilepsy and tuberous sclerosis complex.Epilepsia · 2026Article
- GABACellular and molecular neurobiology · 2026Review
- The Mechanism Underlying the Abnormal Expression of α-Synuclein in the Cortical Lesions of Patients With FCD Type IIb and TSC.CNS neuroscience & therapeutics · 2026Article
- 4-Aminopyridine induced hyperpolarizing oscillations in pediatric human epileptic tissue are network-driven potassium currents that are abolished by activation of KCNQ2-5 (Kv7.2-Kv7.5) channels.Neurobiology of disease · 2026Article
- Focal cortical dysplasias: modeling pediatric drug-resistant epilepsy using human brain organoids.Frontiers in cellular neuroscience · 2026Review
- Article
- Characterizing the Diversity of Layer 2/3 Human Neocortical Neurons in Pediatric Epilepsy.eNeuro · 2025Article
- Somatic mosaicism and interneuron involvement in mTORopathies.Trends in neurosciences · 2025Review
- Multimodal single-cell analyses reveal molecular markers of neuronal senescence in human drug-resistant epilepsy.The Journal of clinical investigation · 2025Article
- Chloride deregulation and GABA depolarization in MTOR-related malformations of cortical development.Brain : a journal of neurology · 2025Article
- Focal postnatal deletion ofFrontiers in molecular neuroscience · 2025Article
- Architecture and cellular composition of focal cortical dysplasia type II: qualitative review of histological studies.Frontiers in cellular neuroscience · 2025Review
- Chronic benzodiazepine treatment triggers gephyrin scaffold destabilization and GABAFrontiers in cellular neuroscience · 2025Article
- Cytoplasmic vacuolization and ectopic formation of perineuronal nets are characteristic pathologies of cytomegalic neurons in tuberous sclerosis.Journal of neuropathology and experimental neurology · 2024Article
- NgfrNature communications · 2024Article
- Balloon cells in malformations of cortical development: friends or foes?Acta epileptologica · 2024Review
- Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer's disease and 5XFAD mice.Brain : a journal of neurology · 2024Article
- GABA system as the cause and effect in early development.Neuroscience and biobehavioral reviews · 2024Review
40 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveThe most common neurological symptom of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) is early life refractory epilepsy. As previous studies have shown enhanced excitatory glutamatergic neurotransmission in TSC and FCD brains, we hypothesized that neurons associated with these lesions may also express altered γ-aminobutyric acid (GABA)(A) receptor (GABA(A)R)-mediated inhibition.
methodsExpression of the GABA(A)R subunits α1 and α4, and the Na(+)-K(+)-2Cl(-) (NKCC1) and the K(+)-Cl(-) (KCC2) transporters, in human TSC and FCD type II specimens were analyzed by Western blot and double label immunocytochemistry. GABA(A) R responses in dysplastic neurons from a single case of TSC were measured by perforated patch recording and compared to normal-appearing cortical neurons from a non-TSC epilepsy case.
resultsTSC and FCD type IIb lesions demonstrated decreased expression of GABA(A)R α1, and increased NKCC1 and decreased KCC2 levels. In contrast, FCD type IIa lesions showed decreased α4, and increased expression of both NKCC1 and KCC2 transporters. Patch clamp recordings from dysplastic neurons in acute slices from TSC tubers demonstrated excitatory GABA(A)R responses that were significantly attenuated by the NKCC1 inhibitor bumetanide, in contrast to hyperpolarizing GABA(A)R-mediated currents in normal neurons from non-TSC cortical slices.
interpretationExpression and function of GABA(A)Rs in TSC and FCD type IIb suggest the relative benzodiazepine insensitivity and more excitatory action of GABA compared to FCD type IIa. These factors may contribute to resistance of seizure activity to anticonvulsants that increase GABAergic function, and may justify add-on trials of the NKCC1 inhibitor bumetanide for the treatment of TSC and FCD type IIb-related epilepsy.
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