{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:43:14Z","timestamp":1791160994619,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,3,23]],"date-time":"2012-03-23T00:00:00Z","timestamp":1332460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>\n                      The 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 \u03b3\u2010aminobutyric acid (GABA)\n                      <jats:sub>A<\/jats:sub>\n                      receptor (GABA\n                      <jats:sub>A<\/jats:sub>\n                      R)\u2010mediated inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Expression of the GABA\n                      <jats:sub>A<\/jats:sub>\n                      R subunits \u03b11 and \u03b14, and the Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010K\n                      <jats:sup>+<\/jats:sup>\n                      \u20102Cl\n                      <jats:sup>\u2212<\/jats:sup>\n                      (NKCC1) and the K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010Cl\n                      <jats:sup>\u2212<\/jats:sup>\n                      (KCC2) transporters, in human TSC and FCD type II specimens were analyzed by Western blot and double label immunocytochemistry. GABA\n                      <jats:sub>A<\/jats:sub>\n                      R responses in dysplastic neurons from a single case of TSC were measured by perforated patch recording and compared to normal\u2010appearing cortical neurons from a non\u2010TSC epilepsy case.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      TSC and FCD type IIb lesions demonstrated decreased expression of GABA\n                      <jats:sub>A<\/jats:sub>\n                      R \u03b11, and increased NKCC1 and decreased KCC2 levels. In contrast, FCD type IIa lesions showed decreased \u03b14, and increased expression of both NKCC1 and KCC2 transporters. Patch clamp recordings from dysplastic neurons in acute slices from TSC tubers demonstrated excitatory GABA\n                      <jats:sub>A<\/jats:sub>\n                      R responses that were significantly attenuated by the NKCC1 inhibitor bumetanide, in contrast to hyperpolarizing GABA\n                      <jats:sub>A<\/jats:sub>\n                      R\u2010mediated currents in normal neurons from non\u2010TSC cortical slices.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation:<\/jats:title>\n                    <jats:p>\n                      Expression and function of GABA\n                      <jats:sub>A<\/jats:sub>\n                      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\u2010on trials of the NKCC1 inhibitor bumetanide for the treatment of TSC and FCD type IIb\u2010related epilepsy. ANN NEUROL 2012\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.22696","type":"journal-article","created":{"date-parts":[[2011,12,16]],"date-time":"2011-12-16T07:00:02Z","timestamp":1324018802000},"page":"539-551","source":"Crossref","is-referenced-by-count":178,"title":["Altered inhibition in tuberous sclerosis and type IIb cortical dysplasia"],"prefix":"10.1002","volume":"71","author":[{"given":"Delia M.","family":"Talos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela","family":"Kosaras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelise","family":"Joseph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca 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