PMID- 25933388
OWN - NLM
STAT- MEDLINE
DCOM- 20150727
LR  - 20181113
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 74
IP  - 6
DP  - 2015 Jun
TI  - The Small-Molecule TrkB Agonist 7, 8-Dihydroxyflavone Decreases Hippocampal 
      Newborn Neuron Death After Traumatic Brain Injury.
PG  - 557-67
LID - 10.1097/NEN.0000000000000199 [doi]
AB  - Previous studies in rodents have shown that after a moderate traumatic brain 
      injury (TBI) with a controlled cortical impact (CCI) device, the adult-born 
      immature granular neurons in the dentate gyrus are the most vulnerable cell type 
      in the hippocampus. There is no effective approach for preventing immature neuron 
      death after TBI. We found that tyrosine-related kinase B (TrkB), a receptor of 
      brain-derived neurotrophic factor (BDNF), is highly expressed in adult-born 
      immature neurons. We determined that the small molecule imitating BDNF, 7, 
      8-dihydroxyflavone (DHF), increased phosphorylation of TrkB in immature neurons 
      both in vitro and in vivo. Pretreatment with DHF protected immature neurons from 
      excitotoxicity-mediated death in vitro, and systemic administration of DHF before 
      moderate CCI injury reduced the death of adult-born immature neurons in the 
      hippocampus 24 hours after injury. By contrast, inhibiting BDNF signaling using 
      the TrkB antagonist ANA12 attenuated the neuroprotective effects of DHF. These 
      data indicate that DHF may be a promising chemical compound that promotes 
      immature neuron survival after TBI through activation of the BDNF signaling 
      pathway.
FAU - Chen, Liang
AU  - Chen L
AD  - From the Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research 
      Institute, and Department of Neurological Surgery, Indiana University School of 
      Medicine, Indianapolis, Indiana (XG, JC); Southern Medical University, Guangzhou 
      China, Guangdong (LC, SZ); and Department of Neurosurgery, 2nd Affiliated 
      Hospital, Fujian Medical University, Quanzhou, China (WH).
FAU - Gao, Xiang
AU  - Gao X
FAU - Zhao, Shu
AU  - Zhao S
FAU - Hu, Weipeng
AU  - Hu W
FAU - Chen, Jinhui
AU  - Chen J
LA  - eng
GR  - R21 NS072631/NS/NINDS NIH HHS/United States
GR  - R21 NS075733/NS/NINDS NIH HHS/United States
GR  - 1R21NS072631-01A/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (6,7-dihydroxyflavone)
RN  - 0 (ANA 12 compound)
RN  - 0 (Azepines)
RN  - 0 (Benzamides)
RN  - 0 (Flavones)
RN  - 0 (Fluoresceins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (fluoro jade)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Azepines/pharmacology
MH  - Benzamides/pharmacology
MH  - Brain Injuries/*drug therapy/*pathology
MH  - Cell Death/drug effects
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Flavones/*therapeutic use
MH  - Fluoresceins
MH  - Hippocampus/drug effects/*pathology
MH  - In Vitro Techniques
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurons/*drug effects
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - Phosphorylation/drug effects
MH  - Receptor, trkB/agonists/antagonists & inhibitors/metabolism
MH  - Signal Transduction/drug effects
PMC - PMC4433561
MID - NIHMS677382
EDAT- 2015/05/02 06:00
MHDA- 2015/07/28 06:00
PMCR- 2016/06/01
CRDT- 2015/05/02 06:00
PHST- 2015/05/02 06:00 [entrez]
PHST- 2015/05/02 06:00 [pubmed]
PHST- 2015/07/28 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - 10.1097/NEN.0000000000000199 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2015 Jun;74(6):557-67. doi: 
      10.1097/NEN.0000000000000199.