PMID- 25404064
OWN - NLM
STAT- MEDLINE
DCOM- 20150914
LR  - 20181113
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 21
IP  - 2
DP  - 2015 Feb
TI  - Basic mechanisms of epileptogenesis in pediatric cortical dysplasia.
PG  - 92-103
LID - 10.1111/cns.12345 [doi]
AB  - Cortical dysplasia (CD) is a neurodevelopmental disorder due to aberrant cell 
      proliferation and differentiation. Advances in neuroimaging have proven effective 
      in early identification of the more severe lesions and timely surgical removal to 
      treat epilepsy. However, the exact mechanisms of epileptogenesis are not well 
      understood. This review examines possible mechanisms based on anatomical and 
      electrophysiological studies. CD can be classified as CD type I consisting of 
      architectural abnormalities, CD type II with the presence of dysmorphic 
      cytomegalic neurons and balloon cells, and CD type III which occurs in 
      association with other pathologies. Use of freshly resected brain tissue has 
      allowed a better understanding of basic mechanisms of epileptogenesis and has 
      delineated the role of abnormal cells and synaptic activity. In CD type II, it 
      was demonstrated that balloon cells do not initiate epileptic activity, whereas 
      dysmorphic cytomegalic and immature neurons play an important role in generation 
      and propagation of epileptic discharges. An unexpected finding in pediatric CD 
      was that GABA synaptic activity is not reduced, and in fact, it may facilitate 
      the occurrence of epileptic activity. This could be because neuronal circuits 
      display morphological and functional signs of dysmaturity. In consequence, drugs 
      that increase GABA function may prove ineffective in pediatric CD. In contrast, 
      drugs that counteract depolarizing actions of GABA or drugs that inhibit the 
      mammalian target of rapamycin (mTOR) pathway could be more effective.
CI  - (c) 2014 John Wiley & Sons Ltd.
FAU - Abdijadid, Sara
AU  - Abdijadid S
AD  - Intellectual and Developmental Disabilities Research Center, Semel Institute for 
      Neuroscience and Human Behavior, University of California Los Angeles, Los 
      Angeles, CA, USA.
FAU - Mathern, Gary W
AU  - Mathern GW
FAU - Levine, Michael S
AU  - Levine MS
FAU - Cepeda, Carlos
AU  - Cepeda C
LA  - eng
GR  - R01 NS038992/NS/NINDS NIH HHS/United States
GR  - R01 NS083823/NS/NINDS NIH HHS/United States
GR  - NS 38992/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20141118
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Brain/*pathology/physiopathology
MH  - Epilepsy/*etiology
MH  - Humans
MH  - Malformations of Cortical Development, Group II/*complications/*pathology
MH  - Neurons/*physiology
MH  - Signal Transduction/physiology
MH  - Sirolimus/metabolism
MH  - gamma-Aminobutyric Acid/metabolism
PMC - PMC4442638
MID - NIHMS691258
OTO - NOTNLM
OT  - Balloon cells
OT  - Cortical dysplasia
OT  - Dysmorphic neurons
OT  - Epileptogenesis
OT  - mTOR pathway
COIS- The authors declare no conflict of interest.
EDAT- 2014/11/19 06:00
MHDA- 2015/09/15 06:00
PMCR- 2014/11/18
CRDT- 2014/11/19 06:00
PHST- 2014/08/18 00:00 [received]
PHST- 2014/09/29 00:00 [revised]
PHST- 2014/10/03 00:00 [accepted]
PHST- 2014/11/19 06:00 [entrez]
PHST- 2014/11/19 06:00 [pubmed]
PHST- 2015/09/15 06:00 [medline]
PHST- 2014/11/18 00:00 [pmc-release]
AID - CNS12345 [pii]
AID - 10.1111/cns.12345 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2015 Feb;21(2):92-103. doi: 10.1111/cns.12345. Epub 2014 Nov 
      18.