PMID- 22435710
OWN - NLM
STAT- MEDLINE
DCOM- 20121227
LR  - 20220309
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Print)
IS  - 0897-7151 (Linking)
VI  - 29
IP  - 12
DP  - 2012 Aug 10
TI  - Estrone is neuroprotective in rats after traumatic brain injury.
PG  - 2209-19
LID - 10.1089/neu.2011.2274 [doi]
AB  - In various animal and human studies, early administration of 17beta-estradiol, a 
      strong antioxidant, anti-inflammatory, and anti-apoptotic agent, significantly 
      decreases the severity of injury in the brain associated with cell death. 
      Estrone, the predominant estrogen in postmenopausal women, has been shown to be a 
      promising neuroprotective agent. The overall goal of this project was to 
      determine if estrone mitigates secondary injury following traumatic brain injury 
      (TBI) in rats. Male rats were given either placebo (corn oil) or estrone 
      (0.5 mg/kg) at 30 min after severe TBI. Using a controlled cortical impact device 
      in rats that underwent a craniotomy, the right parietal cortex was injured using 
      the impactor tip. Non-injured control and sham animals were also included. At 
      72 h following injury, the animals were perfused intracardially with 0.9% saline 
      followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, 
      and stained for TUNEL-positive cells. Estrone decreased cortical lesion volume 
      (p<0.01) and neuronal injury (p<0.001), and it reduced cerebral cortical levels 
      of TUNEL-positive staining (p<0.0001), and decreased numbers of TUNEL-positive 
      cells in the corpus callosum (p<0.03). We assessed the levels of beta-amyloid in the 
      injured animals and found that estrone significantly decreased the cortical 
      levels of beta-amyloid after brain injury. Cortical levels of phospho-ERK1/2 were 
      significantly (p<0.01) increased by estrone. This increase was associated with an 
      increase in phospho-CREB levels (p<0.021), and brain-derived neurotrophic factor 
      (BDNF) expression (p<0.0006). In conclusion, estrone given acutely after injury 
      increases the signaling of protective pathways such as the ERK1/2 and BDNF 
      pathways, decreases ischemic secondary injury, and decreases apoptotic-mediated 
      cell death. These results suggest that estrone may afford protection to those 
      suffering from TBI.
FAU - Gatson, Joshua W
AU  - Gatson JW
AD  - D/FW Center for Resuscitation Research, Department of Surgery, University of 
      Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 
      75390-9160, USA. joshua.gatson@utsw.edu
FAU - Liu, Ming-Mei
AU  - Liu MM
FAU - Abdelfattah, Kareem
AU  - Abdelfattah K
FAU - Wigginton, Jane G
AU  - Wigginton JG
FAU - Smith, Scott
AU  - Smith S
FAU - Wolf, Steven
AU  - Wolf S
FAU - Simpkins, James W
AU  - Simpkins JW
FAU - Minei, Joseph P
AU  - Minei JP
LA  - eng
GR  - P01 AG022550/AG/NIA NIH HHS/United States
GR  - P01 AG027956/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120508
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuroprotective Agents)
RN  - 2DI9HA706A (Estrone)
SB  - IM
MH  - Amyloid beta-Peptides/metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Brain Injuries/*drug therapy/pathology
MH  - Brain-Derived Neurotrophic Factor/biosynthesis
MH  - Cerebral Cortex/injuries/pathology
MH  - Corpus Callosum/metabolism/pathology
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Estrone/*therapeutic use
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - Nerve Growth Factors/biosynthesis
MH  - Neurons/drug effects/pathology
MH  - *Neuroprotective Agents
MH  - Paraffin Embedding
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stereotaxic Techniques
PMC - PMC3960846
EDAT- 2012/03/23 06:00
MHDA- 2012/12/28 06:00
PMCR- 2013/08/10
CRDT- 2012/03/23 06:00
PHST- 2012/03/23 06:00 [entrez]
PHST- 2012/03/23 06:00 [pubmed]
PHST- 2012/12/28 06:00 [medline]
PHST- 2013/08/10 00:00 [pmc-release]
AID - 10.1089/neu.2011.2274 [pii]
AID - 10.1089/neu.2011.2274 [doi]
PST - ppublish
SO  - J Neurotrauma. 2012 Aug 10;29(12):2209-19. doi: 10.1089/neu.2011.2274. Epub 2012 
      May 8.