PMID- 30639357
OWN - NLM
STAT- MEDLINE
DCOM- 20200109
LR  - 20200109
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 71
DP  - 2019 Mar
TI  - Blockade of GluN2B-containing NMDA receptors reduces short-term brain damage 
      induced by early-life status epilepticus.
PG  - 138-149
LID - S0161-813X(18)30234-1 [pii]
LID - 10.1016/j.neuro.2019.01.002 [doi]
AB  - Status epilepticus (SE) during developmental periods can cause short- and 
      long-term consequences to the brain. Brain damage induced by SE is associated to 
      NMDA receptors (NMDAR)-mediated excitotoxicity. This study aimed to investigate 
      whether blockade of GluN2B-containing NMDAR is neuroprotective against SE-induced 
      neurodegeneration and neuroinflammation in young rats. Forty-eight Wistar rats 
      (16 days of life) were injected with pilocarpine (60 mg/kg; i.p.) 12-18 h after 
      LiCl (3 mEq/kg; i.p.). Fifteen minutes after pilocarpine administration, animals 
      received i.p. injections of saline solution (0.9% NaCl; SE + SAL group), ketamine 
      (a non-selective and noncompetitive NMDAR antagonist; 25 mg/kg; SE + KET), 
      CI-1041 (a GluN2B-containing NMDAR antagonist; 10 mg/kg; SE + CI group) or 
      CP-101,606 (a NMDAR antagonist with great selectivity for NMDAR composed by 
      GluN1/GluN2B diheteromers; 10 mg/kg; SE + CP group). Seven days after SE, brains 
      were removed for Fluoro-Jade C staining and Iba1/ED1 immunolabeling. 
      GluN2B-containing NMDAR blockade by CI-1041 or CP-101,606 did not terminate 
      LiCl-pilocarpine-induced seizures. SE + SAL group presented intense 
      neurodegeneration and Iba1(+)/ED1(+) double-labeling in hippocampus (CA1 and 
      dentate gyrus; DG) and amygdala (MePV nucleus). Administration of CP-101,606 did 
      not alter this pattern. However, GluN2B-containing NMDAR blockade by CI-1041 
      reduced neurodegeneration and Iba1(+)/ED1(+) double-labeling in hippocampus and 
      amygdala similar to the reduction observed for SE + KET group. Our results 
      indicate that GluN2B-containing NMDAR are involved in SE-induced 
      neurodegeneration and microglial recruitment and activation, and suggest that 
      stopping epileptic activity is not a condition required to prevent short-term 
      brain damage in young animals.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Loss, Cassio Morais
AU  - Loss CM
AD  - Cellular Neurochemistry Laboratory, Departamento de Bioquimica, Instituto de 
      Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Porto 
      Alegre, Rio Grande do Sul, Brazil; Cellular Biochemistry Laboratory, Departamento 
      de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do 
      Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: 
      cassio.m.loss@gmail.com.
FAU - da Rosa, Nata Sehn
AU  - da Rosa NS
AD  - Cellular Neurochemistry Laboratory, Departamento de Bioquimica, Instituto de 
      Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Porto 
      Alegre, Rio Grande do Sul, Brazil.
FAU - Mestriner, Regis Gemerasca
AU  - Mestriner RG
AD  - Neurorehabilitation and Neural Repair Research Group, Pontificia Universidade 
      Catolica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
FAU - Xavier, Leder Leal
AU  - Xavier LL
AD  - Laboratory of Cell and Tissue Biology, School of Sciences, Pontificia 
      Universidade Catolica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 
      Brazil.
FAU - Oliveira, Diogo Losch
AU  - Oliveira DL
AD  - Cellular Neurochemistry Laboratory, Departamento de Bioquimica, Instituto de 
      Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Porto 
      Alegre, Rio Grande do Sul, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190111
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Benzoxazoles)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 5K3N2D15WW (besonprodil)
SB  - IM
MH  - Animals
MH  - Benzoxazoles/administration & dosage
MH  - Brain/*drug effects/pathology
MH  - Brain Injuries/etiology/*prevention & control
MH  - Encephalitis/etiology/*prevention & control
MH  - Female
MH  - Male
MH  - Microglia/drug effects/metabolism
MH  - Piperidines/administration & dosage
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Status Epilepticus/*complications
OTO - NOTNLM
OT  - CI-1041
OT  - CP-101606
OT  - Development
OT  - Epilepsy
OT  - Neurodegeneration
OT  - Neuroinflammation
EDAT- 2019/01/15 06:00
MHDA- 2020/01/10 06:00
CRDT- 2019/01/15 06:00
PHST- 2018/06/22 00:00 [received]
PHST- 2018/11/22 00:00 [revised]
PHST- 2019/01/09 00:00 [accepted]
PHST- 2019/01/15 06:00 [pubmed]
PHST- 2020/01/10 06:00 [medline]
PHST- 2019/01/15 06:00 [entrez]
AID - S0161-813X(18)30234-1 [pii]
AID - 10.1016/j.neuro.2019.01.002 [doi]
PST - ppublish
SO  - Neurotoxicology. 2019 Mar;71:138-149. doi: 10.1016/j.neuro.2019.01.002. Epub 2019 
      Jan 11.