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IESC transplantation could repair the intestinal barrier after stroke and improve outcomes
Stroke is a leading cause of death, dementia and severe long-term disability. According to the American Heart Association, stroke patients also have a higher risk of depression, which negatively impacts functional and cognitive recovery. The only drug approved by the Food and Drug Administration (FDA) to treat stroke, which is a type of recombinant tissue plasminogen activator, must be administered within a specific time frame after the onset of the stroke and has had limited success. To improve stroke outcomes, scientists at Texas A&M University School of Medicine are pioneering research into the connection between stroke-induced intestinal permeability, or leakage...
IESC transplantation could repair the intestinal barrier after stroke and improve outcomes
Stroke is a leading cause of death, dementia and severe long-term disability. According to the American Heart Association, stroke patients also have a higher risk of depression, which negatively impacts functional and cognitive recovery. The only drug approved by the Food and Drug Administration (FDA) to treat stroke, which is a type of recombinant tissue plasminogen activator, must be administered within a specific time frame after the onset of the stroke and has had limited success. To improve stroke outcomes, scientists at Texas A&M University School of Medicine are pioneering research into the relationship between stroke-induced intestinal permeability, or leakage, and cognitive impairment.
The Texas A&M team investigated the novel idea of whether transplantation of intestinal epithelial stem cells (IESCs) from healthy donors could repair the intestinal barrier after a stroke and improve stroke outcomes. The results of their preclinical study, published in the journal Brain, Behavior, and Immunity, indicate that IESC transplantation reduced stroke-related mortality, reduced dead tissue volume and intestinal permeability, and prevented stroke-related cognitive impairment.
Two-thirds of stroke patients will develop cognitive impairment, while one-third of all stroke patients will develop dementia, according to recent research, so there is an urgent need for more effective stroke therapies that preserve cognitive function after an acute stroke and that remain protective in the following weeks.
Although conventional research into stroke treatment focuses on the brain, the gut responds early and rapidly to stroke with changes that may precede many of the inflammatory events associated with stroke-induced disease. These changes in the intestines, such as B. increased permeability, are likely to result in products synthesized in the intestine entering the bloodstream. Many of these products are toxic and therefore have the potential to increase inflammation and worsen stroke-related brain injuries.
Evidence from a variety of studies shows that IESCs repair the intestine and reduce intestinal permeability. After a stroke, these repair processes can be crucial for maintaining cognitive function.
It is clear that the gut-brain axis is involved in post-stroke injury. Considering the impact of gut health on the brain after a stroke may allow us to advance stroke therapies more effectively.”
Farida Sohrabji, PhD, Regents Professor, Department Head of Neuroscience and Experimental Therapeutics and senior author of the study
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With this in mind, Sohrabji and her team transplanted primary IESCs from healthy post-stroke donors in a preclinical model. IESCs from young donors repaired intestinal architecture and reduced intestinal permeability and consequently reduced blood levels of proteins and other molecules toxic to brain cells. IESC transplantation also prevented depressive-like behaviors and cognitive impairment in the weeks following stroke. IESC transplantation from older donors did not improve stroke outcomes, suggesting that successful transplantation depends on donor age.
This research, still in the preclinical stage, highlights the importance of early therapeutic intervention after stroke and will guide future directions of work. “Future studies will explore refining the dosage and timing of the protocol,” Sohrabji said. “A systematic study of aging stem cells would also be important to explain why older patients suffer more severe strokes.”
Sohrabji, a neuroscientist with significant contributions to the literature on stroke pathogenesis, explained that this preclinical study was led by Kathiresh Kumar Mani, PhD, an associate research scientist in her laboratory. Mani, who is trained in intestinal biology, received a postdoctoral fellowship from the American Heart Association to support this project. The combination of their expertise has enabled them to take stroke therapy research into a new area with exciting results. They also received a generous grant from the WoodNext Foundation, which facilitates their innovative research.
"Ultimately, this research is expected to advance the development of novel therapies that target and repair the intestinal epithelium to ameliorate stroke disability," Sohrabji said, "but the premise - that intestinal stem cells may have therapeutic value outside the intestine - could be considered for a much wider variety of neurological diseases."
Source:
Reference:
Mani, K.K., et al. (2022) Intestinal epithelial stem cell transplantation as a novel therapy for cerebrovascular stroke. Brain behavior and immunity. doi.org/10.1016/j.bbi.2022.10.015.
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