PMID- 33517425
OWN - NLM
STAT- MEDLINE
DCOM- 20211229
LR  - 20211229
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Linking)
VI  - 80
IP  - 3
DP  - 2021 Feb 22
TI  - Neurite Outgrowth Inhibitor (NogoA) Is Upregulated in White Matter Lesions of 
      Complex Cortical Malformations.
PG  - 274-282
LID - 10.1093/jnen/nlaa159 [doi]
AB  - Complex cortical malformations (CCMs), such as hemimegalencephaly and 
      polymicrogyria, are associated with drug-resistant epilepsy and developmental 
      impairment. They share certain neuropathological characteristics including 
      mammalian target of rapamycin (mTOR) activation and an atypical number of white 
      matter neurons. To get a better understanding of the pathobiology of the lesion 
      architecture, we investigated the role of neurite outgrowth inhibitor A (NogoA), 
      a known regulator of neuronal migration. Epilepsy surgery specimens from 16 CCM 
      patients were analyzed and compared with sections of focal cortical dysplasia IIB 
      (FCD IIB, n = 22), tuberous sclerosis complex (TSC, n = 8) as well as healthy 
      controls (n = 15). Immunohistochemistry was used to characterize NogoA, 
      myelination, and mTOR signaling. Digital slides were evaluated automatically with 
      ImageJ. NogoA staining showed a significantly higher expression within the white 
      matter of CCM and FCD IIB, whereas cortical tubers presented levels similar to 
      controls. Further analysis of possible associations of NogoA with other factors 
      revealed a positive correlation with mTOR and seizure frequency. To identify the 
      main expressing NogoA cell type, double staining revealed dysmorphic neuronal 
      white matter cells. Increased NogoA expression is associated with profound 
      inhibition of neuritic sprouting and therefore contributes to a decrease in 
      neuronal network complexity in CCM patients.
CI  - (c) 2021 American Association of Neuropathologists, Inc. All rights reserved.
FAU - Scholl, Theresa
AU  - Scholl T
AD  - From the Department of Pediatrics and Adolescent Medicine, Medical University of 
      Vienna, Vienna, Austria.
FAU - Gruber, Victoria-Elisabeth
AU  - Gruber VE
AD  - From the Department of Pediatrics and Adolescent Medicine, Medical University of 
      Vienna, Vienna, Austria.
FAU - Samueli, Sharon
AU  - Samueli S
AD  - From the Department of Pediatrics and Adolescent Medicine, Medical University of 
      Vienna, Vienna, Austria.
FAU - Lehner, Reinhard
AU  - Lehner R
AD  - Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
FAU - Kasprian, Gregor
AU  - Kasprian G
AD  - Department of Biomedical Imaging and Image-guided Therapy, Medical University of 
      Vienna, Vienna, Austria.
FAU - Czech, Thomas
AU  - Czech T
AD  - Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
FAU - Reinten, Roy J
AU  - Reinten RJ
AD  - Department of Neuropathology, Amsterdam UMC, University of Amsterdam, Amsterdam, 
      The Netherlands.
FAU - Hoogendijk, Lisette
AU  - Hoogendijk L
AD  - Department of Neuropathology, Amsterdam UMC, University of Amsterdam, Amsterdam, 
      The Netherlands.
FAU - Hainfellner, Johannes A
AU  - Hainfellner JA
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Aronica, Eleonora
AU  - Aronica E
AD  - Department of Neuropathology, Amsterdam UMC, University of Amsterdam, Amsterdam, 
      The Netherlands.
AD  - Stichting Epilepsie Instellingen Nederland (SEIN), Zwolle, The Netherlands.
FAU - Muhlebner, Angelika
AU  - Muhlebner A
AD  - Department of Neuropathology, Amsterdam UMC, University of Amsterdam, Amsterdam, 
      The Netherlands.
FAU - Feucht, Martha
AU  - Feucht M
AD  - From the Department of Pediatrics and Adolescent Medicine, Medical University of 
      Vienna, Vienna, Austria.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Nogo Proteins)
SB  - IM
MH  - Adolescent
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Malformations of Cortical Development/*metabolism/*pathology
MH  - Nogo Proteins/*biosynthesis
MH  - Up-Regulation/*physiology
MH  - White Matter/*metabolism/*pathology
OTO - NOTNLM
OT  - Epilepsy surgery
OT  - Hemimegalencephaly
OT  - Polymicrogyria
OT  - White matter pathology
EDAT- 2021/02/01 06:00
MHDA- 2021/12/30 06:00
CRDT- 2021/01/31 20:39
PHST- 2021/02/01 06:00 [pubmed]
PHST- 2021/12/30 06:00 [medline]
PHST- 2021/01/31 20:39 [entrez]
AID - 6124781 [pii]
AID - 10.1093/jnen/nlaa159 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2021 Feb 22;80(3):274-282. doi: 10.1093/jnen/nlaa159.