PMID- 25879397
OWN - NLM
STAT- MEDLINE
DCOM- 20160720
LR  - 20231213
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Linking)
VI  - 32
IP  - 20
DP  - 2015 Oct 15
TI  - Proneurotrophin Binding to P75 Neurotrophin Receptor (P75ntr) Is Essential for 
      Brain Lesion Formation and Functional Impairment after Experimental Traumatic 
      Brain Injury.
PG  - 1599-607
LID - 10.1089/neu.2014.3751 [doi]
AB  - Traumatic brain injury (TBI) initiates an excessive mediator release of e.g. 
      neurotrophins, which promote neuronal survival, differentiation, and modulate 
      synaptic plasticity. Paradoxically, mature forms of neurotrophins promote 
      neuronal survival, whereas unprocessed forms of neurotrophins induce cell death 
      through p75 neurotrophin receptor (p75NTR) signaling. p75NTR is widely expressed 
      during synaptogenesis and is subsequently downregulated in adulthood. Repair 
      mechanisms after acute cerebral insults can reactivate its expression. Therefore, 
      the influence of p75NTR on secondary brain damage was addressed. mRNA levels of 
      p75NTR and its ligands were quantified in brain tissue up to 7 days after 
      experimental TBI (controlled cortical impact; CCI). Brain damage, motor function 
      and inflammatory marker gene expression were determined in mice lacking the 
      proneurotrophin-binding site of the p75NTR protein (NGFR(-/-)) and wild type 
      littermates (NGFR(+/+)) 24 h and 5 days after CCI. In addition, the effect of 
      TAT-Pep5 (pharmacological inhibitor of the intracellular p75NTR death domain) on 
      lesion volume was evaluated 24 h after insult. p75NTR mRNA levels were induced 
      nine-fold by TBI. In NGFR(-/-) mice, lesion volume was reduced by 29% at 24 h and 
      by 21% 5 days after CCI. Motor coordination was significantly improved 24 h after 
      trauma compared with the wild type. Pharmacological inhibition of the p75NTR 
      signaling reduced lesion volume by 18%. The present study presents first time 
      evidence that genetic mutation of the neurotrophin interaction site of p75NTR 
      strongly limits post-traumatic cell death. In addition, we revealed 
      pharmacological targeting of the intracellular p75NTR cell death domain as a 
      promising approach to limit acute brain damage.
FAU - Sebastiani, Anne
AU  - Sebastiani A
AD  - Department of Anesthesiology, University Medical Center of the Johannes 
      Gutenberg-University , Mainz, Germany .
FAU - Golz, Christina
AU  - Golz C
AD  - Department of Anesthesiology, University Medical Center of the Johannes 
      Gutenberg-University , Mainz, Germany .
FAU - Werner, Christian
AU  - Werner C
AD  - Department of Anesthesiology, University Medical Center of the Johannes 
      Gutenberg-University , Mainz, Germany .
FAU - Schafer, Michael K E
AU  - Schafer MK
AD  - Department of Anesthesiology, University Medical Center of the Johannes 
      Gutenberg-University , Mainz, Germany .
FAU - Engelhard, Kristin
AU  - Engelhard K
AD  - Department of Anesthesiology, University Medical Center of the Johannes 
      Gutenberg-University , Mainz, Germany .
FAU - Thal, Serge C
AU  - Thal SC
AD  - Department of Anesthesiology, University Medical Center of the Johannes 
      Gutenberg-University , Mainz, Germany .
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150630
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Ngfr protein, mouse)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Brain Injuries/*drug therapy/*metabolism/pathology/physiopathology
MH  - Cell Death/*drug effects
MH  - Disease Models, Animal
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Protein Binding
MH  - RNA, Messenger/metabolism
MH  - Receptors, Nerve Growth Factor/antagonists & inhibitors/genetics/*metabolism
MH  - Signal Transduction/*drug effects
OTO - NOTNLM
OT  - BDNF
OT  - CCI
OT  - TBI
OT  - neurotrophins, NGF
OT  - p75NTR
OT  - traumatic brain injury
EDAT- 2015/04/17 06:00
MHDA- 2016/07/21 06:00
CRDT- 2015/04/17 06:00
PHST- 2015/04/17 06:00 [entrez]
PHST- 2015/04/17 06:00 [pubmed]
PHST- 2016/07/21 06:00 [medline]
AID - 10.1089/neu.2014.3751 [doi]
PST - ppublish
SO  - J Neurotrauma. 2015 Oct 15;32(20):1599-607. doi: 10.1089/neu.2014.3751. Epub 2015 
      Jun 30.