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Updated: Aug 13, 2026
Ovariectomy and 17β-estradiol Replacement in Rats and Mice: A Visual Demonstration
Published on: June 7, 2012
Estradiol prevents the focal cerebral ischemic injury-induced decrease of forkhead transcription factors
Chung Kil Won1, Hyun Hwa Ji, Phil Ok Koh
1Department of Anatomy, College of Veterinary Medicine and Institute of Animal Medicine, Gyeongsang National University, 900 Gajwa-dong, Jinju 660-701, South Korea.
Abstract:
Estradiol prevents neuronal cell death through the inhibition of apoptotic signals. This study investigated whether estradiol modulates the anti-apoptotic signal through the activation of Akt and its downstream targets, including forkhead transcription factors FKHR and FHKRL1. Adult female rats were ovariectomied and treated with estradiol prior to middle cerebral artery occlusion (MCAO). Brains were collected 24 h after MCAO and infarct volumes were analyzed. Estradiol administration significantly reduced infarct volume and decreased the positive cells of TUNEL staining in the cerebral cortex. Potential activation was measured by phosphorylation of Akt at Ser473, pFKHR at Ser256, and pFKHRL1 at Thr32 using Western blot analysis and immunohistochemistry. Estradiol prevents the injury-induced decrease of pAkt, pFKHR, and pFKHRL1. Further, in the presence of estradiol, the interaction of pFKHRL1 and 14-3-3 increased, compared to that of oil-treated animals. Our findings suggest that estradiol plays a potent protective role against brain injury and that Akt activation and FKHR phosphorylation by estradiol mediated these protective effects.
Insights
Estradiol protects brain cells from injury by activating Akt and its targets, reducing stroke-related damage. This neuroprotective effect involves inhibiting apoptosis and promoting cell survival signaling pathways.
Area of Science:
- Neuroscience
- Endocrinology
- Cell Biology
Background:
- Neuronal cell death is a key factor in brain injury.
- Estradiol is known to inhibit apoptotic signals.
- The specific molecular mechanisms of estradiol's neuroprotection require further elucidation.
Purpose of the Study:
- To investigate if estradiol modulates anti-apoptotic signaling via Akt activation and its downstream targets FKHR and FHKRL1.
- To determine the role of estradiol in protecting against ischemic brain injury.
Main Methods:
- Ovariectomized adult female rats were subjected to middle cerebral artery occlusion (MCAO).
- Estradiol treatment was administered prior to MCAO.
- Infarct volume, TUNEL staining, Western blot analysis, and immunohistochemistry were used to assess neuroprotection and molecular changes.
Main Results:
- Estradiol significantly reduced infarct volume and TUNEL-positive cells in the cerebral cortex.
- Estradiol prevented the decrease in phosphorylation of Akt, FKHR, and FKHRL1 following MCAO.
- Estradiol increased the interaction between phosphorylated FKHRL1 and 14-3-3 protein.
Conclusions:
- Estradiol exerts a potent protective effect against brain injury.
- Akt activation and FKHR phosphorylation are key mediators of estradiol's neuroprotective effects.
- Estradiol's mechanism involves modulating apoptotic and anti-apoptotic signaling pathways.
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