UC Irvine-led study discovers novel cause of brain hemorrhage

In vivo microhemorrhages linked to erythrocyte-brain endothelial interactions.


A groundbreaking study led by the University of California, Irvine, has uncovered a surprising cause of brain hemorrhages that doesn’t involve damage to blood vessels, challenging previous beliefs. The research found that interactions between aged red blood cells and brain capillaries can lead to cerebral microbleeds, shedding light on their formation and suggesting new avenues for treatment and prevention. 

Published in the Journal of Neuroinflammation, the study observed red blood cells stalling in brain capillaries and the subsequent occurrence of hemorrhages. These microbleeds are linked to conditions more common in older adults, such as hypertension, Alzheimer’s disease, and ischemic stroke.

Co-corresponding author Dr. Mark Fisher, professor of neurology at UCI’s School of Medicine, said, “We have previously explored this issue in cell culture systems, but our current study is significant in expanding our understanding of the mechanism by which cerebral microbleeds develop. Our findings may have profound clinical implications, as we identified a link between red blood cell damage and cerebral hemorrhages at the capillary level.”

The research team treated red blood cells with a chemical, tert-butyl hydroperoxide, inducing oxidative stress. After marking the cells with fluorescence, they injected them into mice. The researchers witnessed the red blood cells getting stuck in brain capillaries through two observation methods. Subsequently, a process called endothelial erythrophagocytosis cleared the cells out. As the cells moved out, microglia inflammatory cells engulfed them, triggering the formation of a brain hemorrhage.

Co-corresponding author Xiangmin Xu, UCI professor of anatomy & and neurobiology and director of the campus’s Center for Neural Circuit Mapping, said, “It has always been assumed that for cerebral hemorrhage to occur, blood vessels need to be injured or disrupted. We found that increased red blood cell interactions with the brain capillaries represent an alternative source of development. We need to examine in detail the regulation of brain capillary clearance and also analyze how that process may be related to insufficient blood supply and ischemic stroke, which is the most common form of stroke, to help advance the development of targeted treatments.”

The UC Irvine-led study is pioneering in revealing a non-vascular cause for brain hemorrhages, significantly advancing our understanding of this complex medical phenomenon. This newfound knowledge holds promise for developing innovative therapeutic interventions and preventive measures, marking a crucial step forward in neurology.

Journal reference:

  1. Zhang, H., Sumbria, R.K., Chang, R. et al. Erythrocyte–brain endothelial interactions induce microglial responses and cerebral microhemorrhages in vivo. Journal of Neuroinflammation. DOI: 10.1186/s12974-023-02932-5.
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