We have previously demonstrated that estrogen protects neural tissue from ischemic damage. Estrogen has been shown to increase anti-apoptptic bcl-2 gene expression in nonneural tissue. Bcl-2 is expressed in brain and has been shown to promote neuronal cell survival. Thus, we hypothesized that estrogen enhances expression of bcl-2 after ischemic brain injury. Age-matched male (M), intact female (F), ovariectomized female (O) and estrogen-supplemented ovariectomized (E, via 25-μg slow-release pellets) Wistar rats were subjected to 2 hours of intraluminal middle cerebral artery occlusion, followed by 22 hours of reperfusion. Arterial blood pressure and gases, and rectal and temporalis muscle temperatures were controlled, and laser-Doppler cerebral blood flow (LDF) was monitored to confirm ischemic status. In-situ hybridization of brain slices was performed with a radiolabeled antisense bcl-2 oligonucleotide probe. Control hybridizations were performed with sense and excess unlabeled antisense probes. Slices were apposed to film for 3 wks, covered with emulsion for 6 wks and counterstained with Thionin for histological examination. Bcl-2 signal was concentrated over cells predominantly in the penumbra. Viable cells were scarce in the infarct core with occasional islands of bcl-2-expressing cells. Autoradiographic density was quantified in ischemic cerebral cortex and basal ganglia and expressed as a percentage of optical density on the contralateral side. The results are summarized in the following table (mean ±sem): Group n # slices Cerebral Cortex Basal Ganglia LDF, % ctrl M 4 64 69 ± 20 55 ± 20 31 ± 4 F 4 47 94 ± 4 68 ± 19 40 ± 1 O 2 35 61 ± 39 52 ± 6 36 ± 2 E 2 28 120 ± 0 90 ± 37 48 ± 5 These findings suggest a role for anti-apoptotic bcl-2 gene expression in estrogen-mediated neuroprotection.
|Original language||English (US)|
|Publication status||Published - Mar 20 1998|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology