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Different parvalbumin and GABA expression in human epileptogenic focal cortical dysplasia
Author(s) -
Medici Valentina,
Rossini Laura,
Deleo Francesco,
Tringali Giovanni,
Tassi Laura,
Cardinale Francesco,
Bramerio Manuela,
Curtis Marco,
Garbelli Rita,
Spreafico Roberto
Publication year - 2016
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13405
Subject(s) - cortical dysplasia , parvalbumin , immunocytochemistry , gabaergic , pathology , in situ hybridization , epilepsy , immunostaining , inhibitory postsynaptic potential , lesion , dysplasia , biology , immunohistochemistry , medicine , neuroscience , gene expression , biochemistry , gene
Summary Objective Several studies have reported that inhibitory networks are altered in dysplastic tissue obtained from epilepsy surgery specimens. A consistent decrease in the number of inhibitory interneuronal subpopulation that expresses parvalbumin ( PV ) was reported in postsurgical tissue from patients with focal cortical dysplasia ( FCD ). We tested if the decrease in PV protein expression observed in epileptic tissue corresponds to a parallel impairment in the γ‐aminobutyric acid ( GABA )ergic compartment. Methods We analyzed postsurgical tissue from 30 surgically treated patients who underwent surgery for intractable epilepsy including 26 patients with FCD (types I, II , and III ) and 4 patients without any microscopic visible lesion (cryptogenic) as controls. Serial sections were processed using in situ hybridization with GAD ‐65 and GAD ‐67 probes and immunocytochemistry with antibody against PV . The density of inhibitory PV ‐immunoreactive interneurons in relation to GABA ergic cells was estimated in controls and in all different pathologic groups by using a two‐ and three‐dimensional (2D and 3D) cell‐counting technique. Field fraction and line profile analyses were added to estimate immunostaining proportion and distribution of PV signal generated in gray matter. Results A reduction of PV ‐positive cells and PV ‐immunoreactivity was observed exclusively in FCD type I/ III specimens compared with cryptogenic tissue from control patients with a poor postsurgical outcome. In FCD type II , a profound rearrangement in the cortical distribution of PV immunoreactivity was observed, without a quantitative reduction of the number of neurons and terminals. In situ hybridization did not reveal significant variations of GAD expression in any FCD subtype. Significance Our study suggests a preservation of inhibitory networks in FCD postsurgical tissue, demonstrated by a substantial normal count of GABA ergic neurons. A selective PV expression impairment is demonstrated in FCD type I and III and an abnormal, but not reduced, distribution of PV cells and terminals is confirmed in type II FCD . Possible functional consequences are discussed.