This special feature combines a BHI Trainee Spotlight with a Research Impact Story, highlighting both the achievements of one of our trainees and the impact of their latest publication. Through Jonathan's story, readers can learn about the person behind the research while exploring how his recent findings are advancing our understanding of the brain-heart connection.
Trainees include undergraduate students, graduate students, and postdoctoral fellows who contribute to research. Trainees play many roles at the BHI, not only in their BHI-sponsored research projects, but also serving on committees, participating in events, and more.
Dr. Salazar León and His Research
Dr. Jonathan Salazar León is a postdoctoral fellow in the lab of Dr. Katey Rayner at the University of Ottawa Heart Institute. Jonathan is from Cuernavaca, Morelos, Mexico, where he completed a B.Sc. in biological sciences, an M.Sc. in public health, and a PhD in biomedical science, which focused on energy metabolism and obesity. Building on this expertise, his postdoctoral fellowship in the Rayner Lab, which began in 2022, investigates how an inflammatory, high-cholesterol diet affects brain and heart function in mice.
The Rayner Lab focuses on identifying the biological pathways that drive chronic inflammation—a persistent, dysregulated immune response that no longer serves a beneficial physiological purpose, unlike acute inflammation, which is a short-lived, protective response to stimuli such as infection. The lab then investigates how chronic inflammation contributes to cardiovascular and age-related disorders, with the long-term goal of using this knowledge to develop improved diagnostic tools and treatments for age-related brain-heart diseases.
Chronic inflammation is often present in cardiovascular diseases, including atherosclerosis, a condition in which immune cells and cholesterol build up within the arteries, restricting blood flow. When atherosclerosis affects major arteries, it can disrupt blood flow to critical organs, including the brain. Atherosclerotic plaques that block blood flow to the brain are a major contributor to vascular dementia, the second most common form of dementia after Alzheimer's disease.
In addition to inflammation, factors such as aging and sedentary lifestyle also contribute to atherosclerosis. This is where Jonathan’s research comes in: investigating how high-cholesterol diets negatively impact the vasculature (the body’s network of blood vessels) and, in turn, affect brain function in mice. In June 2026, Jonathan published his first first-author paper detailing these findings in Scientific Reports, a journal published by the Nature Portfolio (1).
Publication: Hyperlipidemia induces hippocampal inflammation and loss of vascularity and can be rescued by silencing RIPK1
Building on their lab’s previous research (2,3), Jonathan and his colleagues sought to understand how a high-cholesterol diet contributes to vascular dysfunction and changes in cognitive function in mice. The study involved feeding mice either a normal or a high-cholesterol diet, designed to mimic aspects of a typical Western diet (processed food). Importantly, the study included both male and female mice in equal numbers.
After 24 weeks on the diet, Jonathan assessed multiple components of vascular health in these mice, including plaque buildup in the major neck arteries that supply the brain (the carotid arteries), blood flow to the brain, and blood vessel density within the brain. He also measured markers of inflammation. Across each measurement, the team found that the high-cholesterol diet worsened vascular outcomes, leading to increased atherosclerosis in the carotid arteries, reduced blood flow, loss of small blood vessels, and increased inflammation in the brain.
Furthermore, and importantly, Jonathan and the team performed a behavioural test in mice that assessed spatial learning and memory. They found that mice fed a high-cholesterol diet performed worse in the behavioural test, indicating impaired cognitive function. Together, these findings demonstrate that a high-cholesterol diet negatively affected vascular health in both the body and brain, increased inflammation, and contributed to poorer cognitive performance. This work demonstrates how cardiovascular risk factors, such as atherosclerosis, can directly influence brain health through the neurovascular system.
The team didn’t stop there. They next investigated a therapeutic target that could prevent these effects in mice. Previous research from the team identified the protein RIPK1 as an important component in the atherosclerosis–inflammation pathway. After 16 weeks on a high-cholesterol diet, the team specifically targeted and reduced RIPK1 protein levels in the mice for an additional 8 weeks, while they remained on the same diet. They found that reducing RIPK1 could prevent the adverse effects associated with the high-cholesterol diet. Carotid artery plaque buildup was reduced, blood flow improved, blood vessel density was restored, and neuroinflammation decreased. Excitingly, the mice also largely regained normal learning and memory performance.
The study suggests that vascular disease caused by high cholesterol intake doesn't just affect the heart and body; it also harms the brain by reducing blood supply and triggering inflammation. These changes may contribute to vascular cognitive impairment, a major contributor to cognitive decline and one of the leading causes of dementia.
Importantly, their work identified RIPK1 as a promising target for future therapies. By targeting RIPK1, future treatments may one day help protect the brain from cognitive decline associated with atherosclerosis and high cholesterol. However, these findings are currently limited to mice, and further research in humans will be needed before this approach can be developed into treatment.
Beyond the Lab Bench: Building Community and Inclusive Science
Beyond the lab and data collection, Jonathan has been an active contributor to the BHI and University of Ottawa community. His brain-heart research has earned recognition through awards and fellowships, including the 2022 Strategic Research Fellowship, Dr. Robert Stelmack Memorial Award, and 2023 Best Poster Award at the Faculty of Medicine Postdoctoral Research Day. More recently, he was awarded both a BHI Fellowship and a Mitacs Fellowship for 2025–2028.
Since 2023, Jonathan has served as an ambassador on the Brain-Heart Interconnectome IDEAS (Inclusion, Diversity, Equity, Accessibility, and Social Justice) committee, working alongside researchers, trainees, and patient partners to promote more inclusive and accessible science. Just as important to Jonathan as research is the connection between science and community. In Mexico, he led workshops designed to bridge the gap between scientists and the public, showcasing what science looks like “beyond the lab bench.”
Through his involvement with the BHI, Jonathan has also deepened his commitment to incorporating diverse perspectives, including patient partner input, into research. He believes that “everyone has their own qualities and can contribute to science in their own way. Science is not limited or restricted; it’s open to everybody.”
This commitment to inclusion has also shaped his research. Through his work with the IDEAS committee and with guidance and support from his supervisor, Jonathan identified an important knowledge gap: the underrepresentation of females in biomedical research. “There’s a lot of lack of information regarding females,” he explains, “I want to focus more on that aspect.”
Therefore, Jonathan has since shifted his research focus to explore how aging and lifestyle factors, including exercise and diet, affect brain-heart health, specifically in menopausal female mice. As Jonathan explains, “Half of the world will have menopause, and yet very little is known about it. I would like to contribute somehow to the topic and be able to help the population in some way.”
He has also incorporated sex- and gender-based analyses into all of his past and future datasets. This work reflects his commitment to advancing more equitable and inclusive research.
Reflections from Dr. Jonathan Salazar León
Beginning his postdoctoral fellowship brought unique challenges for Jonathan, including relocating internationally. Despite this, he encourages trainees to embrace new experiences, noting that an open mind, curiosity, and meaningful connections can turn challenges into opportunities for growth. He is also grateful for the support of his family, who he describes as “the cornerstone of my principles and the source of my motivation to try to help others,” and credits them with giving him the values to keep going through obstacles.
Jonathan also prioritizes creating a welcoming lab environment and maintaining balance through community, physical activity, and personal well-being. He describes the Rayner Lab as a supportive community, with “a sense of community and camaraderie both inside and outside the lab.” He is also grateful to his supervisor, Dr. Katey Rayner, for her support and guidance, and says he has enjoyed working on “Canadian soil,” where he has found people to be very kind.
For aspiring researchers and trainees, Jonathan’s advice begins with self-awareness and finding work that you are passionate about. “It’s important to know yourself, because everyone has their own abilities, strengths, and weaknesses.” He also encourages trainees to look for ways to give back to their communities by identifying gaps where they can contribute through their work.
Above all, Jonathan emphasizes enjoying the journey and embracing new experiences. “Keep moving, keep connecting, and keep learning.” He also encourages trainees not to be afraid of failure: “That’s all part of the process.”
The BHI is grateful for the many talented trainees advancing brain-heart research and looks forward to following their future achievements. Trainees interested in exploring BHI opportunities or becoming a member can visit the Trainee Resource Hub here.
References
- Salazar-Leon J, Freitas-Andrade M, Guadarrama-Perez V, Solari S, Hudak A, Stotts C, et al. Hyperlipidemia induces hippocampal inflammation and loss of vascularity and can be rescued by silencing RIPK1. Sci Rep. 2026 Jun 20. doi:10.1038/s41598-026-54533-w
- Karunakaran D, Nguyen MA, Geoffrion M, Vreeken D, Lister Z, Cheng HS, et al. RIPK1 Expression Associates With Inflammation in Early Atherosclerosis in Humans and Can Be Therapeutically Silenced to Reduce NF-κB Activation and Atherogenesis in Mice. Circulation. 2021 Jan 12;143(2):163–77. doi:10.1161/CIRCULATIONAHA.118.038379
- Karunakaran D, Turner AW, Duchez AC, Soubeyrand S, Rasheed A, Smyth D, et al. RIPK1 gene variants associate with obesity in humans and can be therapeutically silenced to reduce obesity in mice. Nat Metab. 2020 Sep 28;2(10):1113–25. doi:10.1038/s42255-020-00279-2