Research Report Degree and pattern of calbindin immunoreactivity in granule cells of the dentate gyrus differ in mesial temporal sclerosis, cortical malformation- and tumor-related epilepsies Hajnalka Ábrahám a, ⁎ , Zsófia Richter a , Csilla Gyimesi b , Zsolt Horváth c , József Janszky b , Tamás Dóczi c , László Seress a a Central Electron Microscopic Laboratory, Faculty of Medicine, University of Pécs, Szigeti u 12., Pécs, 7624, Hungary b Department of Neurology, Faculty of Medicine, University of Pécs, Rét u. 2., Pécs, 7623, Hungary c Department of Neurosurgery, Faculty of Medicine, University of Pécs, Rét u. 2., Pécs, 7623, Hungary ARTICLE INFO ABSTRACT Article history: Accepted 4 May 2011 Available online 12 May 2011 A loss of calbindin immunoreactivity in granule cells of the hippocampal dentate gyrus is a characteristic feature of temporal lobe epilepsy with hippocampal sclerosis. Whether decreased calbindin expression is unique to the hippocampal sclerosis associated with cryptogenic temporal lobe epilepsy, or also occurs in tumor- or malformation-related epilepsy, is unknown. We show that calbindin immunoreactivity in granule cells has been decreased in epilepsy regardless of its etiology. In cases of cortical malformations or hippocampal sclerosis, calbindin immunoreactivity was undetectable in most granule cells. In tumor-related resections, in patients who had a long history of epileptic seizures, calbindin was detected only in one-third of granule cells. Regardless of etiology, calbindin expression correlated with age of onset and with duration of the epilepsy. In contrast to tumor-induced epilepsy, where calbindin-immunoreactive granule cells were equally distributed in the granule cell layer, in hippocampal sclerosis and malformation-related epilepsy, two-thirds of calbindin-immunoreactive granule cells were located in the outer half and only one-third in the inner half of the layer. Developmentally, granule cells at the border of the molecular layer are ontogenetically the oldest, and those at the border of the hilus are the youngest. The reduction of calbindin immunoreactivity in ontogenetically younger granule cells highlights the deleterious effect of early occurring epilepsy and initial early precipitating injury, including febrile seizures that may substantially affect developing immature granule cells, but less the earlier born matured ones. © 2011 Elsevier B.V. All rights reserved. Keywords: Hippocampal sclerosis Calcium-binding protein Neoplasm Development Pathology 1. Introduction Temporal lobe epilepsy (TLE) is the most common form of focal epilepsies. In many patients (48–75%), therapy-resistant TLE is associated with sclerosis of the medial temporal lobe structures (Blümcke, 2009; Blümcke et al., 2002; Howe et al., 2010; Lehericy et al., 1997), including the hippocampal forma- tion. Less frequently, TLE is related to cortical developmental BRAIN RESEARCH 1399 (2011) 66 – 78 ⁎ Corresponding author at: Central Electron Microscopic Laboratory, Faculty of Medicine, University of Pécs, 7643 Pécs, Szigeti u. 12, Hungary. Postal address: Pécs, 7602, P.O. Box. 99, Hungary. Fax: + 36 72 536 001x1510. E-mail address: hajnalka.abraham@aok.pte.hu (H. Ábrahám). 0006-8993/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2011.05.010 available at www.sciencedirect.com www.elsevier.com/locate/brainres