PMID- 19181336
OWN - NLM
STAT- MEDLINE
DCOM- 20091221
LR  - 20181201
IS  - 1095-8673 (Electronic)
IS  - 0022-4804 (Linking)
VI  - 157
IP  - 2
DP  - 2009 Dec
TI  - 17Beta-estradiol activates adenosine A(2a) receptor after subarachnoid 
      hemorrhage.
PG  - 208-15
LID - 10.1016/j.jss.2008.08.021 [doi]
AB  - BACKGROUND: Our previous study showed that 17beta-estradiol (E2) and an adenosine 
      A(2A) receptor (AR-A(2A)) agonist could attenuate subarachnoid hemorrhage 
      (SAH)-induced cerebral vasospasm via preventing the augmentation of iNOS 
      expression and preserving the normal eNOS expression. This study tests the 
      hypothesis that E2 attenuates SAH-induced vasospasm and apoptosis by activating 
      adenosine AR-A(2A) and extracellular signal-regulated kinase 1 and 2 (ERK1/2), 
      and by altering antiapoptotic and proapoptotic protein expression (Bcl-2 and Bax, 
      respectively). MATERIALS AND METHODS: The two-hemorrhage SAH model in rat was 
      used. Animals were treated with E2 with or without a nonselective estrogen 
      receptor (ER) antagonist (ICI182,780). The cross sectional areas of the basilar 
      artery and terminal dUTP nick-end labeling (TUNEL) were used to determine the 
      degree of vasospasm and apoptosis, respectively. The expressions of Bcl-2, Bax, 
      AR-A(2A), and ERK1/2 in the cerebral cortex, hippocampus, and dentate gyrus were 
      investigated. RESULTS: E2 significantly attenuated vasospasm. Seven days after 
      the first SAH, TUNEL scores were significantly increased, and protein levels of 
      AR-A(2A), ERK1/2, and Bcl-2 were significantly decreased in the dentate gyrus 
      only but not in the cortex and hippocampus. These changes were reversed by E2 
      while ICI182,780 abrogated the antiapoptotic and anti-spastic effects of E2. The 
      expression of Bax did not change in the dentate gyrus after SAH with or without 
      treatment. CONCLUSIONS: The down-regulated AR-A(2A) and ERK may play a role in 
      vasospasm and apoptosis after SAH. The beneficial effect of E2 in the attenuating 
      SAH-induced vasospasm and apoptosis may be due to an increased expression of 
      AR-A(2A) and ERK via ER-dependent mechanisms. These data may support further 
      investigation of E2 in the treatment of SAH in humans.
FAU - Lin, Chih-Lung
AU  - Lin CL
AD  - Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, 
      Taiwan. chihlung1@yahoo.com
FAU - Dumont, Aaron S
AU  - Dumont AS
FAU - Tsai, Yee-Jean
AU  - Tsai YJ
FAU - Huang, Jih-Hui
AU  - Huang JH
FAU - Chang, Kao-Ping
AU  - Chang KP
FAU - Kwan, Aij-Lie
AU  - Kwan AL
FAU - Hong, Yi-Ren
AU  - Hong YR
FAU - Howng, Shen-Long
AU  - Howng SL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081010
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Estrogens)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptor, Adenosine A2A)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Dentate Gyrus/*drug effects/*metabolism/pathology
MH  - Estradiol/analogs & derivatives/*pharmacology/therapeutic use
MH  - Estrogens/*pharmacology
MH  - Fulvestrant
MH  - Male
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Models, Animal
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Adenosine A2A/*metabolism
MH  - Receptors, Estrogen/antagonists & inhibitors
MH  - Subarachnoid Hemorrhage/complications/*metabolism
MH  - Vasospasm, Intracranial/drug therapy/etiology
MH  - bcl-2-Associated X Protein/metabolism
EDAT- 2009/02/03 09:00
MHDA- 2009/12/22 06:00
CRDT- 2009/02/03 09:00
PHST- 2008/05/09 00:00 [received]
PHST- 2008/08/15 00:00 [revised]
PHST- 2008/08/18 00:00 [accepted]
PHST- 2009/02/03 09:00 [entrez]
PHST- 2009/02/03 09:00 [pubmed]
PHST- 2009/12/22 06:00 [medline]
AID - S0022-4804(08)00546-5 [pii]
AID - 10.1016/j.jss.2008.08.021 [doi]
PST - ppublish
SO  - J Surg Res. 2009 Dec;157(2):208-15. doi: 10.1016/j.jss.2008.08.021. Epub 2008 Oct 
      10.