An Interview With Dr. Jaroslaw Aronowski & Dr. Xiurong Zhao

written by Nelson Mills

Dr. Jaroslaw Aronowski has always been curious. As he grew up, this curiosity transformed into a passion for neuroscience research.

“My major interest was always the brain and its serendipity,” Dr. Aronowski said.

Perseverance led Dr. Aronowski to pursue neuroscience at UTHealth, where he now serves as Vice Chair for Research and Roy M. and Phyllis Gough Huffington Chair in Neurology.

For Dr. Xiurong Zhao, neurology research is personal. Her family’s history of hypertension and hemorrhagic stroke piqued her interest in vascular cerebral diseases. Her lab at UTHealth is one of the most advanced in this field, specifically the pathology of intracerebral hemorrhagic stroke (ICH), a serious neurological condition for which effective treatment does not currently exist.

On March 7, 2023, I had the opportunity to interview Dr. Aronowski and Dr. Zhao to learn more about their research interests and relationship with the Houston community.

Dr. Aronowski and Dr. Zhao serve different roles within the Neurology Department at UT Health. Dr. Aronowski mainly spends his day working on papers, mentoring students in the lab, reviewing grants, and staying up to date on medical literature. Passionate about bench work, Dr. Zhao spends her time performing experiments, writing proposals, and performing data analysis. Both Dr. Aronowski and Dr. Zhao employ a variety of models in their research. Among other projects, Dr. Aronowski utilizes in vivo animal studies to research the exchange of mitochondria between astrocytes and neurons. Based on mice’s positive reaction to younger mitochondrial injections, Dr. Aronowski believes that this therapy may be used clinically to improve patients’ cognitive performance.

“When you take mitochondria that are being released by [mice] cells and inject them into animals, the younger mitochondria can actually improve cognitive performance of the animals,” said Dr. Aronowski.

Dr. Zhao recently received NIH funding to study the role of aryl hydrocarbon receptor (AhR) and bilirubin (BrB) in hematoma dissolution after intracerebral hemorrhagic stroke (ICH). After ICH, the subsequent hematoma formation can lead to severe neurological deficits that continue long after the hematoma resolves.

“AhR activation alone or in combination with nuclear factor erythroid 2-related factor 2

(Nrf2) by blood-derived BrB could provide effective protection to microglia/macrophages (MF) for effective hematoma cleanup after ICH. Therefore, activation of AhR could be a novel therapeutic target for ICH,” believes Dr. Zhao.

Both Dr. Aronowski and Dr. Zhao recognize the importance of collaboration in medicine. The Texas Medical Center helps foster this collaboration.

“Having access to a variety of medical science expertise is very useful for generating creative neuroscience research. I believe [the Texas Medical Center] is a great place,” said Dr. Aronowski.

The Texas Medical Center also promotes the formation of relationships between medical institutions and students. Dr. Aronowski and Dr. Zhao view mentoring future generations as an important part of the job, and they have a long history of working with undergraduates (including Rice students), medical students, and research fellows.

To Rice students curious about pursuing neuroscience research, Dr. Aronowski said, “ The best way to recognize [passion for neuroscience] is when it comes naturally. What’s important is that you don’t have to work and you feel that this is part of you.”

Dr. Aronowski’s parting words to young neuroscientists: “Good luck!”

Dr. Zhao’s: “All the best!”

Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that affects over two and a half million people worldwide (NIH). It is characterized by intrusive, repetitive thoughts and behaviors that can cause significant distress and impair daily functioning. Although there are several treatments available for OCD, such as medication and psychotherapy, some individuals do not respond to these treatments. Even worse, they experience intolerable side effects such as the emergence of new symptoms, personality disorders, and suicidal thoughts. In recent years, deep brain stimulation (DBS) has emerged as a promising treatment option for severe and treatment-resistant OCD.

DBS is a surgical procedure that involves implanting electrodes in specific brain regions that are thought to be involved in OCD, such as the anterior cingulate cortex (ACC) and the ventral striatum (VS). The electrodes are connected to a pulse generator that is implanted under the skin in the chest or abdomen. The electrical impulses delivered by the electrodes correct the activity of the targeted brain regions, which can reduce the severity of OCD symptoms.

Several clinical trials have investigated the use of DBS for OCD, with encouraging results. One of the most significant studies was conducted by the National Institute of Mental Health in the United States, which involved 16 participants with severe and treatment-resistant OCD. The study found that DBS significantly reduced the severity of OCD symptoms in all participants, with an average improvement of 40% on the Yale-Brown Obsessive Compulsive Scale (YBOCS), a widely used measure of OCD severity. The effects of DBS were sustained over a long-term follow-up period of up to 10 years, with no significant adverse effects reported (Anholt). Another study conducted in the Netherlands found that DBS effectively reduced OCD symptoms in all six participants, with an average improvement of 46% on the

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YBOCS. The study also found that DBS improved the participants’ quality of life and reduced their anxiety and depression symptoms (Tastevin).

As deep brain stimulation becomes a more prominent approach to OCD, it is important to note that quality of life increases with the approach, making it more convenient than other approaches. Research in our own Houston community is working towards improving the safety and longevity of DBS. Dr. Eric Storch of Baylor College of Medicine reported that “of 352 patients. 66% of patients fully responded to the DBS in the follow-ups” (Gutierrez). Here at Rice, the Neuroengineering Initiative investigates non-invasive deep brain stimulation for multiple psychiatric disorders such as depression and OCD, using computational modeling to see how the stimulation pulses in biological media such as regions of the brain.

While we do not yet know the full story of how DBS treats OCD, it is thought to change the activity of specific neural circuits that are involved in OCD. The ACC is a brain region that is involved in the processing of cognitive and emotional information, and its hyperactivity is thought to contribute to the persistent and distressing nature of OCD symptoms. The VS is part of the brain’s reward system, which is implicated in motivation and pleasure, and its hyperactivity is thought to contribute to the compulsive and repetitive nature of OCD behaviors. Through electric neuromodulation, DBS is thought to change the activity of these areas to a more neurotypical state. Thus, DBS can reduce the severity of OCD symptoms and improve the individual’s quality of life.

Despite the promising results of DBS for OCD, it is still considered an experimental treatment, and its effectiveness and safety are still being evaluated. The surgical procedure carries the risk of bleeding, infection, and other complications, and the electrical stimulation can cause side effects such as headaches, nausea, and cognitive changes. DBS also requires specialized surgical and neuroimaging equipment, as well as a team of experienced clinicians and researchers, making it an expensive and resource-intensive treatment that may not be accessible to all individuals who could potentially benefit from it. Yet, DBS is particularly useful for individuals with severe and treatment-resistant OCD who have not responded to other treatments or who experience intolerable side effects from medication.

Deep Brain Stimulation is a promising treatment option for severe and treatment-resistant OCD that offers a new approach to modulating specific neural circuits that are involved in the disorder. Although it is still an experimental treatment with potential risks and limitations, the available evidence suggests that it can significantly reduce the severity of OCD symptoms and improve the individual’s quality of life. As research in this field continues to advance, it is hoped that DBS will become a more widely available and effective treatment for individuals with OCD.

Anholt GE, van Oppen P, Cath DC, Smit JH, den Boer JA, Verbraak MJ, van Balkom AJ. The yalebrown obsessive-compulsive scale: factor structure of a large sample. Front Psychiatry. 2010 Jul 15;1:18. doi: 10.3389/fpsyt.2010.00018. PMID: 21423429; PMCID: PMC3059660.

Anholt GE, van Oppen P, Cath DC, Smit JH, den Boer JA, Verbraak MJ, van Balkom AJ. The yale-brown obsessive-compulsive scale: factor structure of a large sample. Front Psychiatry. 2010 Jul 15;1:18. doi: 10.3389/fpsyt.2010.00018. PMID: 21423429; PMCID: PMC3059660.

Gutierrez, G. (n.d.). Study finds DBS increasingly viable option for treatment-resistant OCD. Baylor College of Medicine. Retrieved April 9, 2023, from https:// www.bcm.edu/news/study-finds-dbs-increasing ly-viable-option-for-treatment-resistant-ocd

Gutierrez, G. (n.d.). Study finds DBS increasingly viable option for treatment-resistant OCD. Baylor College of Medicine. Retrieved April 9, 2023, from https://www.bcm.edu/ news/study-finds-dbs-increasingly-viable-option-for-treatment-resistant-ocd

Mayo Foundation for Medical Education and Research. (2021, September 3). Deep Brain stimulation. Mayo Clinic. Retrieved April 9, 2023, from https://www.mayoclinic. org/tests-procedures/deep-brain-stimulation/about/ pac-20384562#dialogId45616182

Mayo Foundation for Medical Education and Research. (2021, September 3). Deep Brain stimulation. Mayo Clinic. Retrieved April 9, 2023, from https:// www.mayoclinic.org/tests-procedures/ deep-brain-stimulation/about/pac-20384562#dia logId45616182

Non-invasive deep brain stimulation for various disorders. Behnaam Aazhang. (n.d.). Retrieved April 9, 2023, from https://aaz.rice.edu/deepbrainstimulation/

Non-invasive deep brain stimulation for various disorders. Behnaam Aazhang. (n.d.). Retrieved April 9, 2023, from https://aaz.rice.edu/deepbrainstimula tion/

Tastevin M, Spatola G, Régis J, Lançon C, Richieri R. Deep brain stimulation in the treatment of obsessive-compulsive disorder: current perspectives. Neuropsychiatr Dis Treat. 2019 May 15;15:1259-1272. doi: 10.2147/NDT.S178207. PMID: 31190832; PMCID: PMC6526924.

Tastevin M, Spatola G, Régis J, Lançon C, Richieri

R. Deep brain stimulation in the treatment of obsessive-compulsive disorder: current perspectives. Neuropsychiatr Dis Treat. 2019 May 15;15:1259-1272. doi: 10.2147/NDT.S178207. PMID: 31190832; PMCID: PMC6526924.

U.S. Department of Health and Human Services. (n.d.). Obsessive-compulsive disorder (OCD). National Institute of Mental Health. Retrieved April 9, 2023, from https://www. nimh.nih.gov/health/statistics/obsessive-compulsive-disorder-ocd

U.S. Department of Health and Human Services. (n.d.). Obsessive-compulsive disorder (OCD) National Institute of Mental Health. Retrieved April 9, 2023, from https://www.nimh.nih.gov/health/sta tistics/obsessive-compulsive-disorder-ocd

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