http://stroke.ahajournals.org/content/29/8/1666.short
Abstract
Background and Purpose—We have
previously shown that 17β-estradiol reduces infarction volume in female
rats. The present study determined whether
single injection or chronic implantation of
estrogen confers neuroprotection in male animals with middle cerebral
artery occlusion
(MCAO) and whether there is an interaction with
endogenous testosterone.
Methods—Male Wistar rats were
treated with 2 hours of reversible MCAO. In protocol 1, acute versus
chronic estrogen administration
was examined in groups receiving the following:
Premarin (USP) 1 mg/kg IV, immediately before MCAO (Acute, n=13, plasma
estradiol=171±51
pg/mL); 7 days of 25 μg (E25, n=10, 10±3 pg/mL)
or 100 μg 17β-estradiol (E100, n=12, 69±20 pg/mL) by subcutaneous
implant;
or saline (SAL, n=21, 3±1 pg/mL). Laser-Doppler
flowmetry was used to monitor the ipsilateral parietal cortex throughout
the
ischemic period and early reperfusion. At 22
hours of reperfusion, infarction volume was determined by 0
2,3,5-triphenyltetrazolium
chloride staining and image analysis. In
protocol 2, rats were castrated to deplete endogenous testosterone and
then treated
with estradiol implants: castration only (CAST,
n=13, estradiol=5±2 pg/mL), sham-operated (SHAM, n=10, 4±2 pg/mL),
estradiol
implant 25 μg (CAST+E25, n=16, 7±2 pg/mL) or 100
μg (CAST+E100, n=14, 77±14 pg/mL).
Results—Cortical infarct
volumes were reduced in all estrogen-treated groups: Acute (21±4% of
ipsilateral cortex), E25 (12±5%), and
E100 (12±3%) relative to SAL (38±5%). Caudate
infarction was similarly decreased: Acute (39±7% of ipsilateral
striatum), E25
(25±7%), and E100 (34±6%) relative to SAL
(63±4%). Castration did not alter ischemic outcome; cortical and caudate
infarction
(percentage of respective ipsilateral regions)
were 37±5% and 59±5% in CAST and 39±7% and 57±5% in SHAM, respectively.
Estrogen
replacement reduced infarction volume in
castrated animals in cortex (19±4% in CAST+E25 and 12±4% in CAST+E100)
and in caudate
(42±6% in CAST+25 and 20±7% in CAST+100).
Laser-Doppler flowmetry results during ischemia and reperfusion was not
different
among groups.
Conclusions—Both acute and chronic 17β-estradiol treatments protect male brain in experimental stroke. Testosterone availability does
not alter estradiol-mediated tissue salvage after MCAO.
No comments:
Post a Comment