Summary: Transplantation of intestinal epithelial stem cells from healthy donors reduces stroke-related mortality, reduces the amount of dead brain tissue and intestinal permeability, and prevents stroke-induced cognitive decline.
Source: Texas A&M
Stroke is a leading cause of death, dementia and severe long-term disability. According to the American Heart Association, stroke patients have an increased risk of depression, which negatively affects functional and cognitive recovery.
The only Food and Drug Administration (FDA)-approved drug to treat stroke, such as recombinant tissue plasminogen activator, must be given within a certain time frame after the onset of stroke and has limited success.
To improve stroke outcomes, scientists at the Texas A&M University School of Medicine are conducting pioneering research into the link between stroke-induced intestinal permeability, or looseness, and cognitive impairment.
A Texas A&M team investigated the new idea of whether transplanting intestinal epithelial stem cells (IESCs) from healthy donors could repair the intestinal barrier after stroke and improve stroke outcomes.
The results of their preclinical study published in the journal Brain, behavior and immunityThey indicate that IESC transplantation reduces stroke-related mortality, reduces the amount of dead tissue and intestinal plaque, and prevents stroke-induced cognitive impairment.
As two-thirds of stroke patients develop cognitive impairment, and one-third of all stroke patients develop dementia, recent studies suggest that effective stroke treatments that preserve cognitive function after acute stroke are critical. It will remain defensive in the coming weeks.
Although conventional stroke treatment research has focused on the brain, the gut responds early and rapidly to stroke with changes that may precede stroke-induced disease. These changes in the gut, such as increased permeability, may result in the passage of products synthesized in the gut into the bloodstream.
Many of these products are toxic and therefore increase inflammation and worsen brain damage in the brain.
Evidence from various studies has shown that ISCs repair the gut and reduce intestinal permeability. After stroke, these repair processes may be critical to maintaining cognitive function.
“It is clear that the gut-brain axis is involved in injury after stroke,” said Farida Sohrabji, PhD, Regents Professor, Head of the Department of Neuroscience and Experimental Therapeutics and senior author of the study.
“Impact of gut health on the brain after stroke may allow us to more effectively advance stroke treatments.”
With that in mind, Sohrabji and her team transplanted primary ISCs from healthy donors in a preclinical model after stroke. ISCs from young donors repaired intestinal architecture and reduced intestinal permeability and consequently blood levels of proteins and other molecules toxic to brain cells.
IESC transplants also prevent depression-like behaviors and cognitive impairment in the weeks after stroke. IESC transplants from older donors did not improve stroke outcomes, indicating that successful transplantation depends on the age of the donor.
Still at the pre-clinical stage, this research highlights the importance of early medical intervention after stroke and guides future work directions.
“Future studies will investigate the size and timing of the protocol,” Sohrabji said. “A systematic study of stem cells is important to explain why older patients have more severe strokes.”
Sohrabji, a neuroscientist who has contributed significantly to the literature on stroke pathogenesis, explained that this preclinical study was led by Kateresh Kumar Mani, PhD, an associate research scientist in her lab.
Trained in intestinal biology, Mani received a postdoctoral grant from the American Heart Association in support of this project. Combining their expertise has allowed them to move stroke research into new territory.
They also received a grant from the Woodnext Foundation, which facilitated their innovative research.
“Ultimately, this research is expected to lead to the development of new treatments that target and repair stroke disability,” Sohrabji said. It is considered for many different neurological diseases.
So stroke research news
Author: Leslie Henton
Source: Texas A&M
Contact: Leslie Henton – Texas A&M
Image: The image is in the public domain.
Preliminary study: Open Access.
“Intestinal epithelial stem cell transplantation as a new treatment for cerebrovascular strokeBy Farida Sohrabj and others. Brain, behavior and immunity
Intestinal epithelial stem cell transplantation as a new treatment for cerebrovascular stroke
About 2/3rds Stroke survivors show vascular cognitive impairment and one-third of stroke patients develop dementia 1-3 years after stroke. These dire consequences emphasize the importance of effective stroke treatments.
In addition to the damage to the brain, stroke also rapidly upregulates the intestinal epithelium, resulting in high blood levels of inflammatory cytokines and toxic intestinal metabolites from a ‘leaky’ gut.
We tested whether intestinal repair with intestinal epithelial stem cell (IESC) transplants could improve stroke recovery.
Organoids containing ISCs derived from young mice transplanted into old mice after stroke induced intestinal dysmorphology and reduced intestinal permeability and decreased circulating levels of endotoxin LPS and the inflammatory cytokine IL-17A.
Strikingly, IESC transplants also improved stroke-induced acute (4d) sensory-motor impairment and chronic (30d) cognitive-affective function. Moreover, ISCs from older animals showed sensitizing properties and did not respond to stroke therapy.
These data show the intestine as an important therapeutic target for stroke and demonstrate the efficacy of intestinal stem cell therapy.