PMID- 21463664
OWN - NLM
STAT- MEDLINE
DCOM- 20110913
LR  - 20220408
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 184
DP  - 2011 Jun 16
TI  - Autophagy is involved in traumatic brain injury-induced cell death and 
      contributes to functional outcome deficits in mice.
PG  - 54-63
LID - 10.1016/j.neuroscience.2011.03.021 [doi]
AB  - Previous data demonstrate that traumatic brain injury (TBI) activates autophagy, 
      and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining 
      mainly in neurons. However, the role of autophagy in traumatic brain damage 
      remains elusive. The aim of the present study was to investigate the autophagic 
      mechanisms participating in traumatic brain injury. The autophagy inhibitors 
      3-methyladenine (3-MA) and bafliomycin A1 (BFA) were administered with a single 
      i.c.v. injection before TBI. We first examined the protein levels of Beclin-1 and 
      LC3 II, which have been found to promote autophagy previously. Immunoblotting 
      analysis showed that 3-MA pretreatment reduced post-TBI Beclin-1 and LC3-II 
      levels, and maintained p62/SQSTM1 (p62) levels. In addition, double 
      immunolabeling showed that the increased punctate LC3-II dots colocalizing with 
      Propidium Iodide (PI)-stained nuclei at 24 h after injury, were partially 
      inhibited by 3-MA pretreatment. Furthermore, inhibition of autophagy could reduce 
      TBI-induced cell injury assessed with i.p. injection of PI and lesion volume, and 
      attenuate behavioral outcome evaluated by motor test and Morris water maze. The 
      neuroprotective effects were associated with an inhibition on TBI-induced 
      up-regulation of LC3, Beclin-1, cathepsin B, caspase-3 and the Beclin-1/Bcl-2 
      ratio. Taken together, these data imply that the autophagy pathway is involved in 
      the pathophysiologic responses after TBI, and inhibition of this pathway may help 
      attenuate traumatic damage and functional outcome deficits.
CI  - Copyright (c) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Luo, C-L
AU  - Luo CL
AD  - Department of Forensic Medicine, Shanghai Medical College, Fudan University, 138 
      Yi Xue Yuan Road, Xuhui District, Shanghai 200032, PR China.
FAU - Li, B-X
AU  - Li BX
FAU - Li, Q-Q
AU  - Li QQ
FAU - Chen, X-P
AU  - Chen XP
FAU - Sun, Y-X
AU  - Sun YX
FAU - Bao, H-J
AU  - Bao HJ
FAU - Dai, D-K
AU  - Dai DK
FAU - Shen, Y-W
AU  - Shen YW
FAU - Xu, H-F
AU  - Xu HF
FAU - Ni, H
AU  - Ni H
FAU - Wan, L
AU  - Wan L
FAU - Qin, Z-H
AU  - Qin ZH
FAU - Tao, L-Y
AU  - Tao LY
FAU - Zhao, Z-Q
AU  - Zhao ZQ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110402
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Beclin-1)
RN  - 0 (Becn1 protein, mouse)
RN  - 0 (Map1lc3b protein, mouse)
RN  - 0 (Microtubule-Associated Proteins)
SB  - IM
MH  - Animals
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Autophagy/*physiology
MH  - Beclin-1
MH  - Brain/metabolism/pathology/physiopathology
MH  - Brain Injuries/metabolism/pathology/*physiopathology
MH  - Cell Death/*physiology
MH  - Male
MH  - Maze Learning/*physiology
MH  - Mice
MH  - Microtubule-Associated Proteins/metabolism
MH  - Neurons/metabolism/physiology
EDAT- 2011/04/06 06:00
MHDA- 2011/09/14 06:00
CRDT- 2011/04/06 06:00
PHST- 2010/11/11 00:00 [received]
PHST- 2011/03/06 00:00 [revised]
PHST- 2011/03/14 00:00 [accepted]
PHST- 2011/04/06 06:00 [entrez]
PHST- 2011/04/06 06:00 [pubmed]
PHST- 2011/09/14 06:00 [medline]
AID - S0306-4522(11)00279-X [pii]
AID - 10.1016/j.neuroscience.2011.03.021 [doi]
PST - ppublish
SO  - Neuroscience. 2011 Jun 16;184:54-63. doi: 10.1016/j.neuroscience.2011.03.021. 
      Epub 2011 Apr 2.