PMID- 24849663
OWN - NLM
STAT- MEDLINE
DCOM- 20140926
LR  - 20211021
IS  - 1559-7016 (Electronic)
IS  - 0271-678X (Print)
IS  - 0271-678X (Linking)
VI  - 34
IP  - 8
DP  - 2014 Aug
TI  - Neuroprotection after traumatic brain injury in heat-acclimated mice involves 
      induced neurogenesis and activation of angiotensin receptor type 2 signaling.
PG  - 1381-90
LID - 10.1038/jcbfm.2014.93 [doi]
AB  - Long-term exposure of mice to mild heat (34 degrees C+/-1 degrees C) confers neuroprotection 
      against traumatic brain injury (TBI); however, the underling mechanisms are not 
      fully understood. Heat acclimation (HA) increases hypothalamic angiotensin II 
      receptor type 2 (AT2) expression and hypothalamic neurogenesis. Accumulating data 
      suggest that activation of the brain AT2 receptor confers protection against 
      several types of brain pathologies, including ischemia, a hallmark of the 
      secondary injury occurring following TBI. As AT2 activates the same pro-survival 
      pathways involved in HA-mediated neuroprotection (e.g., Akt phosphorylation, 
      hypoxia-inducible factor 1alpha (HIF-1alpha), and brain-derived neurotrophic factor 
      (BDNF)), we examined the role of AT2 in HA-mediated neuroprotection after TBI. 
      Using an AT2-specific antagonist PD123319, we found that the improvements in 
      motor and cognitive recovery as well as reduced lesion volume and neurogenesis 
      seen in HA mice were all diminished by AT2 inhibition, whereas no significant 
      alternations were observed in control mice. We also found that nerve growth 
      factor/tropomyosin-related kinase receptor A (TrkA), BDNF/TrkB, and HIF-1alpha 
      pathways are upregulated by HA and inhibited on PD123319 administration, 
      suggesting that these pathways play a role in AT2 signaling in HA mice. In 
      conclusion, AT2 is involved in HA-mediated neuroprotection, and AT2 activation 
      may be protective and should be considered a novel drug target in the treatment 
      of TBI patients.
FAU - Umschweif, Gali
AU  - Umschweif G
AD  - 1] Department of Pharmacology, School of Pharmacy, Institute of Drug Research, 
      Jerusalem, Israel [2] Laboratory of Environmental Physiology, The Hebrew 
      University of Jerusalem, Jerusalem, Israel.
FAU - Shabashov, Dalia
AU  - Shabashov D
AD  - Department of Pharmacology, School of Pharmacy, Institute of Drug Research, 
      Jerusalem, Israel.
FAU - Alexandrovich, Alexander G
AU  - Alexandrovich AG
AD  - Department of Pharmacology, School of Pharmacy, Institute of Drug Research, 
      Jerusalem, Israel.
FAU - Trembovler, Victoria
AU  - Trembovler V
AD  - Department of Pharmacology, School of Pharmacy, Institute of Drug Research, 
      Jerusalem, Israel.
FAU - Horowitz, Michal
AU  - Horowitz M
AD  - Laboratory of Environmental Physiology, The Hebrew University of Jerusalem, 
      Jerusalem, Israel.
FAU - Shohami, Esther
AU  - Shohami E
AD  - Department of Pharmacology, School of Pharmacy, Institute of Drug Research, 
      Jerusalem, Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140521
PL  - United States
TA  - J Cereb Blood Flow Metab
JT  - Journal of cerebral blood flow and metabolism : official journal of the 
      International Society of Cerebral Blood Flow and Metabolism
JID - 8112566
RN  - 0 (Angiotensin II Type 2 Receptor Blockers)
RN  - 0 (Imidazoles)
RN  - 0 (Pyridines)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 130663-39-7 (PD 123319)
SB  - IM
MH  - *Acclimatization
MH  - Angiotensin II Type 2 Receptor Blockers/pharmacology
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - Brain Injuries/metabolism/physiopathology/*prevention & control
MH  - Disease Models, Animal
MH  - Head Injuries, Closed/metabolism/physiopathology/*prevention & control
MH  - *Hot Temperature
MH  - Imidazoles/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Motor Activity/physiology
MH  - *Neurogenesis
MH  - Pyridines/pharmacology
MH  - Receptor, Angiotensin, Type 2/*metabolism
MH  - Signal Transduction
PMC - PMC4126099
EDAT- 2014/05/23 06:00
MHDA- 2014/09/27 06:00
PMCR- 2015/08/01
CRDT- 2014/05/23 06:00
PHST- 2014/03/06 00:00 [received]
PHST- 2014/04/23 00:00 [revised]
PHST- 2014/04/30 00:00 [accepted]
PHST- 2014/05/23 06:00 [entrez]
PHST- 2014/05/23 06:00 [pubmed]
PHST- 2014/09/27 06:00 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - jcbfm201493 [pii]
AID - 10.1038/jcbfm.2014.93 [doi]
PST - ppublish
SO  - J Cereb Blood Flow Metab. 2014 Aug;34(8):1381-90. doi: 10.1038/jcbfm.2014.93. 
      Epub 2014 May 21.