PMID- 23174180
OWN - NLM
STAT- MEDLINE
DCOM- 20130724
LR  - 20130128
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 51
DP  - 2013 Mar
TI  - AT2-receptor stimulation enhances axonal plasticity after spinal cord injury by 
      upregulating BDNF expression.
PG  - 177-91
LID - S0969-9961(12)00371-3 [pii]
LID - 10.1016/j.nbd.2012.11.008 [doi]
AB  - It is widely accepted that the angiotensin AT2-receptor (AT2R) has 
      neuroprotective features. In the present study we tested pharmacological 
      AT2R-stimulation as a therapeutic approach in a model of spinal cord compression 
      injury (SCI) in mice using the novel non-peptide AT2R-agonist, Compound 21 (C21). 
      Complementary experiments in primary neurons and organotypic cultures served to 
      identify underlying mechanisms. Functional recovery and plasticity of 
      corticospinal tract (CST) fibers following SCI were monitored after application 
      of C21 (0.3mg/kg/dayi.p.) or vehicle for 4 weeks. Organotypic co-culture of 
      GFP-positive entorhinal cortices with hippocampal target tissue served to 
      evaluate the impact of C21 on reinnervation. Neuronal differentiation, apoptosis 
      and expression of neurotrophins were investigated in primary murine astrocytes 
      and neuronal cells. C21 significantly improved functional recovery after SCI 
      compared to controls, and this significantly correlated with the increased number 
      of CST fibers caudal to the lesion site. In vitro, C21 significantly promoted 
      reinnervation in organotypic brain slice co-cultures (+50%) and neurite outgrowth 
      of primary neurons (+25%). C21-induced neurite outgrowth was absent in neurons 
      derived from AT2R-KO mice. In primary neurons, treatment with C21 further induced 
      RNA expression of anti-apoptotic Bcl-2 (+75.7%), brain-derived neurotrophic 
      factor (BDNF) (+53.7%), the neurotrophin receptors TrkA (+57.4%) and TrkB 
      (+67.9%) and a marker for neurite growth, GAP43 (+103%), but not TrkC. Our data 
      suggest that selective AT2R-stimulation improves functional recovery in 
      experimental spinal cord injury through promotion of axonal plasticity and 
      through neuroprotective and anti-apoptotic mechanisms. Thus, AT2R-stimulation may 
      be considered for the development of a novel therapeutic approach for the 
      treatment of spinal cord injury.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Namsolleck, Pawel
AU  - Namsolleck P
AD  - Center for Cardiovascular Research, Institute of Pharmacology, 
      Charite-Universitatsmedizin Berlin, Hessische Str. 3-4, 10115 Berlin, Germany.
FAU - Boato, Francesco
AU  - Boato F
FAU - Schwengel, Katja
AU  - Schwengel K
FAU - Paulis, Ludovit
AU  - Paulis L
FAU - Matho, Katherine S
AU  - Matho KS
FAU - Geurts, Nathalie
AU  - Geurts N
FAU - Thone-Reineke, Christa
AU  - Thone-Reineke C
FAU - Lucht, Kristin
AU  - Lucht K
FAU - Seidel, Kerstin
AU  - Seidel K
FAU - Hallberg, Anders
AU  - Hallberg A
FAU - Dahlof, Bjorn
AU  - Dahlof B
FAU - Unger, Thomas
AU  - Unger T
FAU - Hendrix, Sven
AU  - Hendrix S
FAU - Steckelings, U Muscha
AU  - Steckelings UM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121119
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptor, Angiotensin, Type 2)
SB  - IM
MH  - Animals
MH  - Axons/metabolism
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - Disease Models, Animal
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nerve Regeneration/drug effects
MH  - Neuronal Plasticity/drug effects/*physiology
MH  - Neuroprotective Agents/pharmacology
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptor, Angiotensin, Type 2/*agonists
MH  - Recovery of Function/drug effects
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Spinal Cord Injuries/*metabolism
MH  - Up-Regulation
EDAT- 2012/11/24 06:00
MHDA- 2013/07/25 06:00
CRDT- 2012/11/24 06:00
PHST- 2012/06/19 00:00 [received]
PHST- 2012/10/22 00:00 [revised]
PHST- 2012/11/09 00:00 [accepted]
PHST- 2012/11/24 06:00 [entrez]
PHST- 2012/11/24 06:00 [pubmed]
PHST- 2013/07/25 06:00 [medline]
AID - S0969-9961(12)00371-3 [pii]
AID - 10.1016/j.nbd.2012.11.008 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2013 Mar;51:177-91. doi: 10.1016/j.nbd.2012.11.008. Epub 2012 Nov 
      19.