From the Department of Anesthesiology and Critical Care Medicine, Johns
Hopkins University School of Medicine, Baltimore, Md.
Correspondence to Patricia D. Hurn, PhD, Department of Anesthesiology and Critical Care Medicine, 600 N Wolfe St, Blalock 1404, Baltimore, MD 21287. E-mail phurn{at}welchlink.welch.jhu.edu
Background and Purpose—We have
previously shown that 17ß-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 17ß-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 17ß-estradiol treatments
protect male brain in experimental stroke. Testosterone availability
does not alter estradiol-mediated tissue salvage after MCAO.
Department
of Surgery and Physiology,
Mayo Foundation,
Rochester, Minnesota
{hd1}References
© 1998 American Heart Association, Inc.
Original Contributions
Estrogen-Mediated Neuroprotection After Experimental Stroke in Male Rats
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P. M. Wise, M. J. Smith, D. B. Dubal, M. E. Wilson, K. M. Krajnak, and K. L. Rosewell Neuroendocrine Influences and Repercussions of the Menopause Endocr. Rev., June 1, 1999; 20(3): 243 - 248. [Abstract] [Full Text]
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T. J. Toung, A. Bhardwaj, V. L. Dawson, T. M. Dawson, R. J. Traystman, P. D. Hurn, and P. H. Chan Neuroprotective FK506 Does Not Alter In Vivo Nitric Oxide Production During Ischemia and Early Reperfusion in Rats • Editorial Comment Stroke, June 1, 1999; 30(6): 1279 - 1285. [Abstract] [Full Text] [PDF]
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Q. Wang, R. Santizo, V. L. Baughman, D. A. Pelligrino, and C. Iadecola Estrogen Provides Neuroprotection in Transient Forebrain Ischemia Through Perfusion-Independent Mechanisms in Rats • Editorial Comment Stroke, March 1, 1999; 30(3): 630 - 637. [Abstract] [Full Text] [PDF]
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