PMID- 28647536
OWN - NLM
STAT- MEDLINE
DCOM- 20180612
LR  - 20200930
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Linking)
VI  - 79
IP  - Pt B
DP  - 2017 Oct 3
TI  - CRHR1 exacerbates the glial inflammatory response and alters BDNF/TrkB/pCREB 
      signaling in a rat model of global cerebral ischemia: implications for 
      neuroprotection and cognitive recovery.
PG  - 234-248
LID - S0278-5846(17)30234-8 [pii]
LID - 10.1016/j.pnpbp.2017.06.021 [doi]
AB  - This study examined the impact of corticotropin-releasing hormone type 1 receptor 
      (CRHR1) blockade using Antalarmin (ANT) on the expression of markers of 
      neuroplasticity and inflammation, as well as neuroprotection and behavioral 
      recovery following global cerebral ischemia. Male Wistar rats (N=50) were treated 
      with ANT (2mug/2mul; icv) or a vehicle solution prior to a sham or four vessel 
      (4VO) occlusion. Seven days post ischemia, anxiety was assessed in the Elevated 
      Plus Maze and Open Field tests, and fear and spatial learning in a Y-Maze Passive 
      Avoidance Task and the Barnes Maze. Thirty days post ischemia, brain derived 
      neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) receptor 
      expression, hippocampal neuronal death and inflammation were determined by 
      analyzing immunoreactivity (ir) of neuron-specific nuclear protein (NeuN), 
      microglia (IBA1, ionized calcium binding adaptor molecule 1), astrocytes (GFAP, 
      glial fibrillary acidic protein) and TNFalpha (tumor necrosis factor alpha) a 
      pro-inflammatory cytokine. Our findings revealed that ANT improved behavioral 
      impairments, while conferring neuroprotection and blunting neuroinflammation in 
      all hippocampal sub-regions post ischemia. We also observed reduced BDNF and TrkB 
      mRNA and protein levels at the hippocampus, and increased expression at the 
      hypothalamus and amygdala post ischemia, site-specific alterations which were 
      regularized by pre-ischemic CRHR1 blockade. These findings support that CRHR1 
      actively contributes to altered brain plasticity, neuronal inflammation and 
      injury and recovery of function following ischemic brain insults.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - de la Tremblaye, Patricia B
AU  - de la Tremblaye PB
AD  - Behavioural Neuroscience Group, School of Psychology, University of Ottawa, 136 
      Jean-Jacques Lussier, Ottawa, ON K1N 6N5, Canada.
FAU - Benoit, Simon M
AU  - Benoit SM
AD  - Behavioural Neuroscience Group, School of Psychology, University of Ottawa, 136 
      Jean-Jacques Lussier, Ottawa, ON K1N 6N5, Canada.
FAU - Schock, Sarah
AU  - Schock S
AD  - Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth 
      Rd, Ottawa, ON K1H 8N5, Canada.
FAU - Plamondon, Helene
AU  - Plamondon H
AD  - Behavioural Neuroscience Group, School of Psychology, University of Ottawa, 136 
      Jean-Jacques Lussier, Ottawa, ON K1N 6N5, Canada. Electronic address: 
      hplamond@uottawa.ca.
LA  - eng
PT  - Journal Article
DEP - 20170621
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Central Nervous System Agents)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Corticotropin-Releasing Hormone)
RN  - 0 (antalarmin)
RN  - 5CLY6W2H1M (CRF receptor type 1)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Anxiety/immunology/pathology
MH  - Brain/drug effects/*immunology/pathology
MH  - Brain Ischemia/*immunology/psychology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Central Nervous System Agents/pharmacology
MH  - Cognition/drug effects/*physiology
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Disease Models, Animal
MH  - Male
MH  - Neuroglia/drug effects/*immunology
MH  - Neuroimmunomodulation/drug effects/physiology
MH  - Neuronal Plasticity/drug effects/physiology
MH  - Neuroprotection/drug effects/*physiology
MH  - Pyrimidines/pharmacology
MH  - Pyrroles/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats, Wistar
MH  - Receptor, trkB/metabolism
MH  - Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors/*metabolism
MH  - Recovery of Function/drug effects/physiology
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Antalarmin
OT  - Anxiety
OT  - BDNF
OT  - Global cerebral ischemia
OT  - Inflammation
OT  - Memory
EDAT- 2017/06/26 06:00
MHDA- 2018/06/13 06:00
CRDT- 2017/06/26 06:00
PHST- 2017/03/27 00:00 [received]
PHST- 2017/06/12 00:00 [revised]
PHST- 2017/06/21 00:00 [accepted]
PHST- 2017/06/26 06:00 [pubmed]
PHST- 2018/06/13 06:00 [medline]
PHST- 2017/06/26 06:00 [entrez]
AID - S0278-5846(17)30234-8 [pii]
AID - 10.1016/j.pnpbp.2017.06.021 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):234-248. doi: 
      10.1016/j.pnpbp.2017.06.021. Epub 2017 Jun 21.