Dr. Brann has documented estrogen receptors on astrocytes, which makes them appear to be targets for estrogen action, and found the astrocytes may have an unexpected role in regulating reproductive function. TGF-b also enhances connectivity of the GnRH neurons and protects them from cell death. Estrogen has been shown to reduce the stroke injury in animal models, but when Dr. Brann adds physiological levels of estrogen to neurons from the cerebral cortex, estrogen can't protect the neurons. This suggests that some other cell type is necessary to mediate the protective effect and that the cell type may be the astrocyte, he said. He's already looked at tamoxifen, a common treatment and preventive drug for breast cancer, and plans to look at raloxifene, a common treatment for osteoporosis which also is being studied for its effectiveness in preventing breast cancer.
Tamoxifen reduces stroke infarct size in middle cerebral artery occluded ovariectomized rats.
Like estrogen, tamoxifen may be targeting the estrogen receptors on the star-like astrocytes. If he pre-treats the cells with physiological doses of estradiol or tamoxifen such as the amount a patient might get for breast cancer the cells still die. But when these substances are given to an intact brain complete with astrocytes many cells survive. With the recent renewal grant, Dr. Brann will do more studies in the intact brain, trying to identify whether astrocytes, or some other type of cell, are responsible for survival of neurons and if the release of growth factor is how they do it. All rights reserved.