PMID- 25862938
OWN - NLM
STAT- MEDLINE
DCOM- 20160328
LR  - 20181113
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Print)
IS  - 0969-9961 (Linking)
VI  - 78
DP  - 2015 Jun
TI  - Neuroprotective role of an N-acetyl serotonin derivative via activation of 
      tropomyosin-related kinase receptor B after subarachnoid hemorrhage in a rat 
      model.
PG  - 126-33
LID - S0969-9961(15)00107-2 [pii]
LID - 10.1016/j.nbd.2015.01.009 [doi]
AB  - N-[2-(5-hydroxy-1H-indol-3-yl) ethyl]-2-oxopiperidine-3-carboxamide (HIOC), an 
      N-acetyl serotonin derivative, selectively activates tropomyosin-related kinase 
      receptor B (TrkB). This study is to investigate a potential role of HIOC on 
      ameliorating early brain injury after experimental subarachnoid hemorrhage (SAH). 
      One hundred and fifty-six adult male Sprague-Dawley rats were used. SAH model was 
      induced by endovascular perforation. TrkB small interfering RNA (siRNA) or 
      scramble siRNA was injected intracerebroventricularly 24h before SAH. HIOC was 
      administrated intracerebroventricularly 3h after SAH and compared with 
      brain-derived neurotrophic factor (BDNF). SAH grade and neurologic scores were 
      evaluated for the outcome study. For the mechanism study, the expression of TrkB, 
      phosphorylated TrkB (p-TrkB), phosphorylated extracellular signal regulated 
      kinase (p-ERK), B-cell lymphoma 2 (Bcl-2) and cleaved caspase 3 (CC3) was 
      detected by Western blots, and neuronal injury was determined by double 
      immunofluorescence staining of neuronal nuclei and terminal deoxynucleotidyl 
      transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling. Knocking 
      down of TrkB decreased the expression of Bcl-2 and aggravated neurologic deficits 
      24h after SAH. HIOC activated TrkB/ERK pathway, decreased neuronal cell death, 
      and improved neurobehavioral outcome, and these effects were abolished by TrkB 
      siRNA. HIOC was more potent than BDNF in reduction of apoptosis 24h post-SAH. 
      Thus, we conclude that administration of HIOC activated TrkB/ERK signaling 
      cascade and attenuated early brain injury after SAH. HIOC may be a promising 
      agent for further treatment for SAH and other stroke events.
CI  - Copyright (c) 2015. Published by Elsevier Inc.
FAU - Tang, Junjia
AU  - Tang J
AD  - Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, Zhejiang, China; Departments of Physiology and 
      Pharmacology, Loma Linda University, Loma Linda, CA, USA.
FAU - Hu, Qin
AU  - Hu Q
AD  - Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, 
      CA, USA.
FAU - Chen, Yujie
AU  - Chen Y
AD  - Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, 
      CA, USA.
FAU - Liu, Fei
AU  - Liu F
AD  - Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, 
      CA, USA.
FAU - Zheng, Yun
AU  - Zheng Y
AD  - Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, 
      CA, USA.
FAU - Tang, Jiping
AU  - Tang J
AD  - Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, 
      CA, USA.
FAU - Zhang, Jianmin
AU  - Zhang J
AD  - Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, 
      Zhejiang University, Hangzhou, Zhejiang, China. Electronic address: 
      zjm135@vip.sina.com.
FAU - Zhang, John H
AU  - Zhang JH
AD  - Departments of Physiology and Pharmacology, Loma Linda University, Loma Linda, 
      CA, USA. Electronic address: johnzhang3910@yahoo.com.
LA  - eng
GR  - R01 NS081740/NS/NINDS NIH HHS/United States
GR  - R01 NS084921/NS/NINDS NIH HHS/United States
GR  - NS081740/NS/NINDS NIH HHS/United States
GR  - NS084921/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 - 20150408
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Brain/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Disease Models, Animal
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - Neurons/metabolism
MH  - Neuroprotective Agents/*administration & dosage
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/agonists/*metabolism
MH  - Serotonin/*administration & dosage/*analogs & derivatives
MH  - Subarachnoid Hemorrhage/*metabolism/*prevention & control
PMC - PMC4545490
MID - NIHMS679235
OTO - NOTNLM
OT  - Apoptosis
OT  - Brain-derived neurotrophic factor
OT  - Early brain injury
OT  - N-acetyl serotonin derivative
OT  - Subarachnoid hemorrhage
OT  - Tropomyosin-related kinase receptor B
EDAT- 2015/04/12 06:00
MHDA- 2016/03/29 06:00
PMCR- 2016/06/01
CRDT- 2015/04/12 06:00
PHST- 2014/10/23 00:00 [received]
PHST- 2014/12/27 00:00 [revised]
PHST- 2015/01/30 00:00 [accepted]
PHST- 2015/04/12 06:00 [entrez]
PHST- 2015/04/12 06:00 [pubmed]
PHST- 2016/03/29 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - S0969-9961(15)00107-2 [pii]
AID - 10.1016/j.nbd.2015.01.009 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2015 Jun;78:126-33. doi: 10.1016/j.nbd.2015.01.009. Epub 2015 Apr 
      8.