Dr. Louise D. McCullough is a physician-scientist with a longstanding interest in vascular physiology, neuro-inflammation, cerebrovascular disease, sex differences in stroke, and aging. She is currently the Chair of the Department of Neurology. A practicing vascular neurologist, she has clinical expertise in stroke prevention, acute stroke treatment, sex differences in stroke, and outcome assessment. Together with five other scientists, Dr. McCullough has formed the BRAINS Research Laboratory that is heavily focused on understanding the mechanisms of stroke pathogenesis with the aim of identifying novel targets for therapeutic development in both the acute and long-term treatments of stroke. In addition to 6 primary faculty, there are a large number of collaborating faculty in departments at McGovern Medical School, throughout the Texas Medical Center, and around the country.
Dr. McCullough, along with the other principal investigators in the BRAINS Research Laboratory, has extensively studied the differences between males and females in ischemic stroke. We have demonstrated that males and females display significant differences in cell death mechanisms following an ischemic stroke. These basic molecular studies have a direct translational relevance, as treatments that have shown an efficacy in one sex have paradoxically shown a detrimental effect in the other. As a result, the BRAINS Research Laboratory has emphasized the importance of utilizing male and female animals in all of our stroke studies, which the NIH has since implemented in grant applications, recognizing and accounting for sex as a biological variable. This observation has been corroborated later in clinical trials. Over the past decade, the sexual dimorphism in response to pharmacological therapies has been increasingly accepted not just in stroke, but in the renal, immune, cardiac and stem cell fields.
In the context of sex differences following an ischemic stroke, our group has made an effort to better understand the roles of chromosomal and hormonal influences. We have demonstrated a protective role of estrogen in stroke, as young females are more protected against ischemic stroke compared to males. Furthermore, this protective effect is lost after the hormonal levels of estrogen decreases (menopause), making females more susceptible to brain damage. The BRAINS Research Laboratory is a leader in the field. Dr. Liu and Dr. McCullough have been working to determine the chromosomal and hormonal contributions to cell death.
Additional research in the BRAINS Research Laboratory focuses on understanding the link between ischemic stroke, disordered breathing and subsequent cognitive decline. Research from Dr. Li’s group have produced a model of post-stroke disordered breathing often witnesses in human stroke survivors through a murine model of middle cerebral artery occlusion that produces a form of disordered breathing. Currently, we are examining the link between respiratory dysfunction, marked by apneas, and long-term cognitive decline. Preliminary evidence suggests that pharmacologic manipulation of central respiratory control sites stabilize breathing by eliminating apneas and therefore potentially improving cognitive outcomes.
Stroke is primarily a disease of the elderly, and with an expanding aging population, the BRAINS Research Laboratory has been developing a stroke model in aged animals. This approach allows us to model stroke in the context of aging, which is a more accurate representation of what is seen in the clinic. This also helps us determine novel and promising targets for new therapeutic approaches. We have identified new molecules in our aged stroke model which we have targeted and found to improve stroke recovery in animal models. Current experiments are attempting to reduce age-related inflammation to reduce brain damage after stroke. These results have driven us to examine sex and age-related differences in both stroke mechanism and recovery, an area that is the focus of Dr. Li’s and Dr. Venna’s program.
In addition, the BRAINS Research Laboratory is currently focusing on understanding the gut microbiome distribution and it’s close communication with the intestinal epithelium in shaping human health with respect to age related diseases. Dr. Ganesh has formed a “Biome Group” together with Dr. McCullough and Dr. Venu to examine the key role gut bacterial dysbiosis plays in stroke outcomes via intestinal epithelial damage. Furthermore, they are extending this knowledge into other age related disease like Parkinson’s disease and Alzheimer’s disease to understand how microbial molecular mechanisms can beneficially be manipulated for better health outcomes.
Research in Dr. Sean P. Marrelli’s group focuses on pharmacological hypothermia through activation of TRPV1 channels following stroke and the role of endothelial TRPV1 channels in regulating cerebral blood flow in the injured region following stroke. Additionally, his group is investigating the role of endothelium-derived von Willebrand Factor (VWF) strings in post-stroke thrombosis and whether pharmacologically disrupting VWF string formation can improve post-stroke perfusion and functional outcome.
A final area of interest is directly inspired by patients experience in the clinic. Why do some patient’s recover well, while others do not, even with the same stroke severity and comorbidities? Evidence from clinical studies have shown that psychosocial factors strongly influence stroke outcomes. Patients with high levels of social support exhibit more rapid and extensive functional recovery after stroke when compared to socially isolated individuals. Additionally, perceived social isolation predicts high morbidity and mortality in cerebrovascular disease. We have demonstrated these same effects using animal models, showing that socially isolated mice develop severe brain damage after stroke compared to those that are housed with a healthy cage mate. BRAINS Research Laboratory is focusing on understanding how psychosocial factors produces changes in inflammation that can influence stroke recovery, as well as, recognizing molecular changes, as a method to identify potential biomarkers, that will allow clinicians to give an adequate diagnosis and treatment to patients. Working with trainers from the School of Nursing, ongoing clinical studies are working to evaluate how optimism can affect stroke recovery.
The BRAINS Research Laboratory is a multifaceted group with many interests and projects that stem from the core focus of stroke, aging, inflammation, recovery, neuro-degeneration, and sex-differences. The lab has multiple principal investigators, who offer their knowledge and expertise to post-doctoral fellows and graduate students. There is a strong environment of independence in the lab, which in part, allows for almost each individual to work on their own project or segment of a larger project. In conjunction with independent labs, the BRAINS Research Laboratory collaborates and works as a team; each individual possesses a unique skill set that they want to share with others both within the group and throughout UTHealth here in Houston. The BRAINS Research Laboratory serves as a home for over 42 investigators, research scientist, research fellows and assistants, graduate, medical and undergraduate students. Come visit us on the 3rd floor of the Medical School building and Medical School Extension Building!