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We evaluated a series of focal cortical dysplasia (<jats:styled-content style=\"fixed-case\">FCD<\/jats:styled-content>,<jats:italic><jats:styled-content style=\"fixed-case\">n<\/jats:styled-content><\/jats:italic>\u2009=\u200926; type<jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>) and tuberous sclerosis complex (<jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>,<jats:italic><jats:styled-content style=\"fixed-case\">n<\/jats:styled-content><\/jats:italic>\u2009=\u20096) cases. Sections were processed for terminal deoxynucleotidyl transferase\u2010mediated 2\u2032\u2010deoxyuridine 5\u2032\u2010triphosphate nick\u2010end labeling (<jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content>) labeling and immunohistochemistry using markers for the evaluation of apoptosis signaling pathways and neurodegeneration\u2010related proteins\/pathways. In both<jats:styled-content style=\"fixed-case\">FCD II<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>specimens, we observed significant increases in both<jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content>\u2010positive and caspase\u20133\u2010positive cells compared with controls and<jats:styled-content style=\"fixed-case\">FCD I<\/jats:styled-content>. Expression of<jats:styled-content style=\"fixed-case\">\u03b2<\/jats:styled-content>\u2010amyloid precursor protein was observed in neuronal soma and processes in<jats:styled-content style=\"fixed-case\">FCD II<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>. In these specimens, we also observed an abnormal expression of death receptor\u20106. Immunoreactivity for phosphorylated tau was only found in older patients with<jats:styled-content style=\"fixed-case\">FCD II<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>. In these cases, prominent nuclear\/cytoplasmic p62 immunoreactivity was detected in both dysmorphic neurons and balloon\/giant cells. Our data provide evidence of complex, but similar, mechanisms of cell injury in focal malformations of cortical development associated with mammalian target of rapamycin pathway hyperactivation, with prominent induction of apoptosis\u2010signaling pathways and premature activation of mechanisms of neurodegeneration.<\/jats:p>","DOI":"10.1111\/bpa.12060","type":"journal-article","created":{"date-parts":[[2013,4,16]],"date-time":"2013-04-16T08:36:42Z","timestamp":1366101402000},"page":"1-17","source":"Crossref","is-referenced-by-count":48,"title":["Cell injury and Premature Neurodegeneration in Focal Malformations of Cortical Development"],"prefix":"10.1111","volume":"24","author":[{"given":"Anand","family":"Iyer","sequence":"first","affiliation":[{"name":"Department of (Neuro)Pathology Academic Medical Center University of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avanita","family":"Prabowo","sequence":"additional","affiliation":[{"name":"Department of (Neuro)Pathology Academic Medical Center University of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Anink","sequence":"additional","affiliation":[{"name":"Department of (Neuro)Pathology Academic Medical Center University of Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim G. 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