The milestone was recorded by Google Scholar, which tracks citations in scholarly literature, including articles, books, theses and abstracts, etc.
Another citation index, Thomson Reuters’ Web of Science, has counted 471 citations for the article. By comparison, the median number of citations for papers on neuroscience and behavior that were written that year is 34.5.
The much-cited article, by senior author Lydia L. DonCarlos, PhD, and colleagues, was published in the January 2001 issue of Progress in Neurobiology. It is titled “Neuroprotection by Estradiol.” (Estradiol is one of the estrogen hormones.) It was among the first comprehensive reviews of the potential protective effects of estrogen on the brain.
The article detailed how estrogen “decreases the risk and delays the onset and progression of Alzheimer’s disease and schizophrenia, and may also enhance recovery from traumatic neurological injury such as stroke.”
Since publication, further data from the Women’s Health Initiative and other studies have refined scientists’ understanding of the benefits and risks of estrogen exposure, DonCarlos said. The Loyola University Health System neuroendocrinologist has written subsequent review articles about estrogen and the brain.
Estrogen can protect against dementia and other neurological disorders by decreasing inflammatory responses and by enhancing cells’ ability to survive damage. “It’s a natural way for the brain to protect itself, since the brain normally makes neuroprotective estradiol in response to injury,” DonCarlos said.
But there also are risks. The Women’s Health Initiative found that taking estrogen plus progestin increased women’s risks of heart disease, blood clots, stroke and breast cancer.
DonCarlos and other researchers are studying agents called selective estrogen receptor modulators (SERMs) that potentially could provide the benefits of estrogen without the risks. One such agent is tamoxifen, which reduces the risk of breast cancer by blocking estrogen receptors in the breast. In the bones, tamoxifen has the opposite effect by acting like estrogen and thus reducing the risk of osteoporosis, DonCarlos said.
“We are looking for other SERMs that potentially could help protect the brain, without increasing the risk of breast cancer or other negative effects,” DonCarlos said.
Most studies suggest that estrogen has beneficial effects on cognitive function, DonCarlos said. “But we still have a lot of research to do before recommending use of estrogens in the clinic for this purpose.”
DonCarlos is a professor in the Department of Cell and Molecular Physiology at Loyola University Chicago Stritch School of Medicine. Her co-authors on the 2001 paper are Luis Miguel Garcia-Segura (first author), a professor at the Instituto Cajal in Madrid and past president of the Spanish Society for Neuroscience, and Iñigo Azcoitia, associate professor of biology at the Universidad Complutense of Madrid.
Based in the western suburbs of Chicago, Loyola University Health System is a quaternary care system with a 61-acre main medical center campus, the 36-acre Gottlieb Memorial Hospital campus and 28 primary and specialty care facilities in Cook, Will and DuPage counties. The medical center campus is conveniently located in Maywood, 13 miles west of the Chicago Loop and 8 miles east of Oak Brook, Ill. The heart of the medical center campus, Loyola University Hospital, is a 569-licensed-bed facility. It houses a Level 1 Trauma Center, a Burn Center and the Ronald McDonald® Children’s Hospital of Loyola University Medical Center. Also on campus are the Cardinal Bernardin Cancer Center, Loyola Outpatient Center, Center for Heart & Vascular Medicine and Loyola Oral Health Center as well as the LUC Stritch School of Medicine, the LUC Marcella Niehoff School of Nursing and the Loyola Center for Fitness. Loyola’s Gottlieb Memorial Hospital campus in Melrose Park includes the 264-bed community hospital, the Gottlieb Center for Fitness and the Marjorie G. Weinberg Cancer Care Center.