Understanding the Link Between HIV and Brain Health
Dec. 11, 2024
People with HIV, even those on effective treatment, are more vulnerable to cerebral small vessel disease (CSVD), especially as they age. This disorder can cause strokes, memory problems, and other cognitive difficulties.
New research supported by the National Institute of Neurological Disorders and Stroke and led by University of Rochester Medical Center (URMC) neurologist Giovanni Schifitto, MD, and cardiovascular biologist Jinjiang Pang, MD, PhD, will focus on Delta-like 4 protein (DII4) hypothesized to play a key role in the deterioration of the microscopic network of blood vessels that serve the brain.
Giovanni Schifitto, MD
Schifitto and his colleagues have been studying how chronic inflammation in people with HIV—and more recently, people recovering from long COVID—drives cerebrovascular disease and disrupts the structure and connections between different parts of the brain.
Schifitto and collaborators, including Nasir Uddin, PhD, Mia Weber, PhD, and Xing Qiu, PhD, have been focused on developing new neuroimaging biomarkers that will help researchers better measure the effectiveness of treatments for neuroinflammatory, neurodegenerative, and cerebrovascular disorders, like CSVD.
The team co-authored a paper last month in the journal Scientific Reports describing their work to improve the detection of the subtle brain microstructural changes associated with HIV infection using advanced MRI techniques. They showed that an imaging modality called tensor-valued imaging did best in identifying damage in the brain strongly associated with cognitive impairment, suggesting that this technique could be a new sensitive biomarker for HIV-associated neurocognitive disorders.
Jinjiang Pang, MD, PhD
The new research focusing on Dll4 will employ novel imaging techniques to assess brain microcirculation. Although DII4 is typically expressed in blood vessel endothelial cells, it can also be released by immune cells called monocytes. People with HIV, despite effective antiretroviral treatments, have persistent systemic inflammation and high levels of DII4 in their blood.
Pang’s research in animal models has shown that Dll4 can modify blood vessels’ integrity. The project aims to better understand how monocyte-derived Dll4 affects blood vessels in the brain and how it is related to brain injury and, ultimately, cognitive decline in people with HIV. In vitro studies using blood cells from people with and without HIV will target molecular mechanisms that regulate monocyte-derived DII4 expression and interaction with blood vessels.
The team believes that this research's findings could help scientists ultimately develop new treatments to prevent or treat CSVD in people with HIV. Since aging is a factor associated with monocyte activation, the findings from this study are potentially generalizable to the aging population.
Additional members of the team include Hongmei Yang, PhD, in Biostatistics and Computational Biology, and Shumin Wang, PhD, in the Pang Lab.
Author
Mark Michaud
(585) 273-4790
mark_michaud@urmc.rochester.edu
Contact
Mark F. Michaud,
Mark_Michaud@URMC.Rochester.edu
University of Rochester Medical Center (URMC)
Source: https://www.urmc.rochester.edu/news/story/understanding-the-link-between-hiv-and-brain-health
"Reproduced with permission - University of Rochester Medical Center (URMC)"
University of Rochester Medical Center (URMC)
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