PMID- 24117347
OWN - NLM
STAT- MEDLINE
DCOM- 20131231
LR  - 20211021
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 54
IP  - 11
DP  - 2013 Nov
TI  - AMPA receptor antagonist NBQX attenuates later-life epileptic seizures and 
      autistic-like social deficits following neonatal seizures.
PG  - 1922-32
LID - 10.1111/epi.12378 [doi]
AB  - PURPOSE: To determine whether AMPA receptor (AMPAR) antagonist NBQX can prevent 
      early mammalian target of rapamycin (mTOR) pathway activation and long-term 
      sequelae following neonatal seizures in rats, including later-life spontaneous 
      recurrent seizures, CA3 mossy fiber sprouting, and autistic-like social deficits. 
      METHODS: Long-Evans rats experienced hypoxia-induced neonatal seizures (HS) at 
      postnatal day (P)10. NBQX (20 mg/kg) was administered immediately following HS 
      (every 12 h x 4 doses). Twelve hours post-HS, we assessed mTOR activation marker 
      phosphorylated p70-S6 kinase (p-p70S6K) in hippocampus and cortex of vehicle (HS 
      + V) or NBQX-treated post-HS rats (HS + N) versus littermate controls (C + V). 
      Spontaneous seizure activity was compared between groups by epidural cortical 
      electroencephalography (EEG) at P70-100. Aberrant mossy fiber sprouting was 
      measured using Timm staining. Finally, we assessed behavior between P30 and P38. 
      KEY FINDINGS: Postseizure NBQX treatment significantly attenuated seizure-induced 
      increases in p-p70S6K in the hippocampus (p < 0.01) and cortex (p < 0.001). 
      Although spontaneous recurrent seizures increased in adulthood in HS + V rats 
      compared to controls (3.22 +/- 1 seizures/h; p = 0.03), NBQX significantly 
      attenuated later-life seizures (0.14 +/- 0.1 seizures/h; p = 0.046). HS + N rats 
      showed less aberrant mossy fiber sprouting (115 +/- 8.0%) than vehicle-treated 
      post-HS rats (174 +/- 10%, p = 0.004), compared to controls (normalized to 100%). 
      Finally, NBQX treatment prevented alterations in later-life social behavior; 
      post-HS rats showed significantly decreased preference for a novel over a 
      familiar rat (71.0 +/- 12 s) compared to controls (99.0 +/- 15.6 s; p < 0.01), 
      whereas HS + N rats showed social novelty preference similar to controls (114.3 +/- 
      14.1 s). SIGNIFICANCE: Brief NBQX administration during the 48 h postseizure in 
      P10 Long-Evans rats suppresses transient mTOR pathway activation and attenuates 
      spontaneous recurrent seizures, social preference deficits, and mossy fiber 
      sprouting observed in vehicle-treated adult rats after early life seizures. These 
      results suggest that acute AMPAR antagonist treatment during the latent period 
      immediately following neonatal HS can modify seizure-induced activation of mTOR, 
      reduce the frequency of later-life seizures, and protect against CA3 mossy fiber 
      sprouting and autistic-like social deficits.
CI  - Wiley Periodicals, Inc. (c) 2013 International League Against Epilepsy.
FAU - Lippman-Bell, Jocelyn J
AU  - Lippman-Bell JJ
AD  - Department of Neurology, Children's Hospital Boston and Harvard Medical School, 
      Boston, Massachusetts, U.S.A; Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, Pennsylvania, U.S.A.
FAU - Rakhade, Sanjay N
AU  - Rakhade SN
FAU - Klein, Peter M
AU  - Klein PM
FAU - Obeid, Makram
AU  - Obeid M
FAU - Jackson, Michele C
AU  - Jackson MC
FAU - Joseph, Annelise
AU  - Joseph A
FAU - Jensen, Frances E
AU  - Jensen FE
LA  - eng
GR  - NS 031718/NS/NINDS NIH HHS/United States
GR  - DP1 OD003347/OD/NIH HHS/United States
GR  - P01 NS038475/NS/NINDS NIH HHS/United States
GR  - R56 NS031718/NS/NINDS NIH HHS/United States
GR  - P20 NS080181/NS/NINDS NIH HHS/United States
GR  - F32 NS068161/NS/NINDS NIH HHS/United States
GR  - P30 HD18655/HD/NICHD NIH HHS/United States
GR  - P30 HD018655/HD/NICHD NIH HHS/United States
GR  - R01 NS031718/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131001
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Quinoxalines)
RN  - 0 (Receptors, AMPA)
RN  - 118876-58-7 (2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline)
SB  - IM
MH  - Aging
MH  - Animals
MH  - Animals, Newborn
MH  - Autistic Disorder/drug therapy
MH  - Behavior, Animal/drug effects/physiology
MH  - Disease Models, Animal
MH  - Hippocampus/drug effects/metabolism/pathology
MH  - Male
MH  - Neurons/*metabolism
MH  - Quinoxalines/*pharmacology
MH  - Rats
MH  - Rats, Long-Evans
MH  - Receptors, AMPA/*antagonists & inhibitors/metabolism
MH  - Seizures/chemically induced/*drug therapy/metabolism
PMC - PMC4262152
MID - NIHMS522536
OTO - NOTNLM
OT  - AMPA receptor antagonists
OT  - Autistic-like behavior
OT  - Early life seizures
OT  - Epileptogenesis
OT  - Hypoxic/ischemic encephalopathy
EDAT- 2013/10/15 06:00
MHDA- 2014/01/01 06:00
PMCR- 2014/12/10
CRDT- 2013/10/15 06:00
PHST- 2013/08/15 00:00 [accepted]
PHST- 2013/10/15 06:00 [entrez]
PHST- 2013/10/15 06:00 [pubmed]
PHST- 2014/01/01 06:00 [medline]
PHST- 2014/12/10 00:00 [pmc-release]
AID - 10.1111/epi.12378 [doi]
PST - ppublish
SO  - Epilepsia. 2013 Nov;54(11):1922-32. doi: 10.1111/epi.12378. Epub 2013 Oct 1.