title: Disorganization of neocortical lamination in focal cortical dysplasia is brain-region dependent: evidence from layer-specific marker expression.
abstract: BACKGROUND
  Focal cortical dysplasias (FCD) are local disturbances of neocortical architecture and a common cause of pharmaco-resistant focal epilepsy. Little is known about the pathomechanisms leading to architectural abnormalities associated with FCD.
  
  
  RESULTS
  In the present study we compared 52 FCD cases originating from the frontal or temporal lobe with or without Ammon's horn sclerosis (AHS) with regard to structural and molecular differences. We applied layer-specific (ER81, RORß, SMI32, TLE4) and interneuron (calbindin, parvalbumin) markers by means of immunohistochemistry, in situ hybridization (ISH), and real time RT-PCR and correlated our findings with clinical parameters. We found that: (1) Structural abnormalities were most prominent in layers III-VI including changed morphology of individual neurons or dispersion, blurring and thinning of layers. These alterations were most pronounced in isolated frontal FCD, whereas the most homogeneous group was FCD IIIa. (2) Numbers of calbindin- and parvalbumin-positive interneurons varied considerably within the different FCD groups, but were not generally reduced. A significant decrease was only found for calbindin-positive interneurons in frontal FCD, and for parvalbumin-positive interneurons in FCD IIIa. (3) Interestingly, FCD IIIa presented with significant changes in the numbers of calbindin- or TLE4-positive neurons when compared to isolated FCD or controls. (4) Correlations between clinical and cellular parameters strongly depended on FCD localisation and age of the patients.
  
  
  CONCLUSIONS
  In summary, our data suggest that late cortical development is disturbed in FCD, yet most likely by different causes depending on brain region, FCD type and FCD severity.
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery, University of Freiburg, Breisacherstr, 64, Freiburg 79106, Germany. carola.haas@uniklinik-freiburg.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Fauser
authors.forename: Ute
authors.initials: U
authors.lastname: Häussler
authors.forename: Catharina
authors.initials: C
authors.lastname: Donkels
authors.forename: Susanne
authors.initials: S
authors.lastname: Huber
authors.forename: Julia
authors.initials: J
authors.lastname: Nakagawa
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulze-Bonhage
authors.forename: Josef
authors.initials: J
authors.lastname: Zentner
authors.forename: Carola A
authors.initials: CA
authors.lastname: Haas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064026:Calbindins / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D054220:Malformations of Cortical Development / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012598:Sclerosis; D012720:Severity of Illness Index; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D064026:Calbindins; D009687:Nuclear Proteins; D010320:Parvalbumins; D012097:Repressor Proteins; C465817:TLE4 protein, human