Not all strokes are created equal: College of Medicine researcher studies how age and sex affect recovery from stroke

While men are not actually from Mars and women do not hail from Venus, the two genders can be very different when it comes to medical conditions. In the case of stroke, for example, young women have the lowest incidence of stroke, while older women have more strokes than men and don’t recover as well.

Why is this? And could understanding these gender and age differences in stroke lead to better treatments?

These are the questions that Farida Sohrabji, PhD, professor and associate chair of the Department of Neuroscience and Experimental Therapeutics in the Texas A&M College of Medicine, is trying to answer.

Sohrabji says one reason that men and women have different risks for stroke may be due to the type of hormones they make and the fact that levels of these hormones change with age. Young women, for example, have high amounts of estrogen, but estrogen levels decline as women age.

This led many researchers to believe that giving estrogen therapy to older women might reduce their risk for stroke, but in reality, studies showed that estrogen treatment could increase stroke risk. Additionally, Sohrabji and her colleagues found that administering estrogen treatment to middle-aged female rats actually made the stroke worse, and caused more brain tissue to die – an outcome that she attributes to the fact that estrogen is not the only hormone that declines as women age.

“Estrogen is the most obvious one because menopause is a huge event in women’s lives so we pay a lot of attention to it and we know a lot about it, but in reality a lot of other endocrine organs are changing,” she says.

Among the other hormones that decline as women become older is a peptide hormone made by the liver called Insulin-like Growth Factor-1 (IGF-1), which plays a key role in the growth of cells and blood vessels.

“IGF-1 levels also go down with age, so essentially in middle-aged women you have a double whammy – low estrogen and low IGF-1,” Sohrabji says.

Sohrabji’s lab has shown that if you give older, estrogen-treated females IGF-1, the combined effect is reduced brain cell death after stroke.

“IGF-1 works wonders when given four hours after a stroke,” Sohrabji says. “It virtually shrinks the size of the infarct (tissue death). We are very excited about the potential this therapy has for use in patients.”

Unfortunately, administering IGF-1 for long periods of time can cause tumors, so the research team must continue searching for alternate therapies that could be used alone or in conjunction with IGF-1.

One potential novel therapy involves exploiting very small RNA molecules that are known as microRNA (miRNA). More than 2,000 different miRNA molecules exist, and each plays a key role in determining what proteins get made in the body.

Sohrabji has discovered that one of these miRNA salvages brain tissue when it is injected intravenously after stroke in older female animals. She believes that microRNA could eventually be a viable stroke therapy.

To further test her theory, Sohrabji has been working with a local group of emergency department physicians to collect blood samples from women who have had strokes and are willing to participate in a research study. By discovering which miRNAs are expressed in patients with good outcomes versus those with bad outcomes, researchers may be able to develop a targeted therapy that will improve the outcome for patients who don’t have enough of the “good” miRNA.

The need for new stroke treatments is great because right now, tissue plasminogen activator (tPA) is the only option available and it must be administered within a four-and-a-half hour window after occurrence of a stroke.

“Because some of the symptoms of stroke are different in women than men, many women may be misdiagnosed and may not be eligible in time for tPA therapy,” Sohrabji says. She also notes that since many older women live alone, they are less likely to have someone who can take them to an emergency room.

Sohrabji’s research on women and stroke is part of a growing field known as gender-specific medicine that seeks to exploit naturally occurring differences in age and sex to develop new treatments. She believes her research may have applications to other diseases in which estrogen plays a role.

Sohrabji has received more than $2.5 million in funding from the National Institute on Aging, the National Institute of Neurologic Diseases and Stroke, and the Office of Research on Women’s Health