Repair the intestines after stroke and save brain function

Stroke is a leading cause of
death, dementia and severe long-term disability.
According to the American Heart Association, stroke patients are also at greater risk of depression, which negatively
affects both function and cognitive recovery.
The only stroke drug approved by the U.
S.
Food and Drug Administration (FDA) is a recombinant tissue plasminogen activator that must be given for a specific time after the onset of the stroke and has limited
efficacy.
To improve stroke outcomes, scientists at Texas A&M University School of Medicine are pioneering research into the link
between stroke-induced intestinal permeability, or leakage, and cognitive impairment.

The Texas A&M University team investigated a new idea of whether transplanting 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, show that IESC transplantation reduces stroke-related mortality, reduces the volume of dead tissue and intestinal leakage, and prevents stroke-induced cognitive impairment
.

According to recent research, two-thirds of stroke patients will develop cognitive impairment, while one-third of stroke patients will develop dementia, so there is an urgent need for more effective stroke therapies that maintain cognitive function after an acute stroke and maintain a protective effect
in the weeks that follow.

While traditional stroke treatment research has focused on the brain, the gut responds to stroke early and rapid, and its changes may precede many of the inflammatory events
associated with stroke-induced disease.
These changes in the intestine, such as increased permeability, can cause products synthesized in the intestine to enter the bloodstream
.
Many of these products are toxic, so they increase inflammation and exacerbate brain damage
caused by stroke.

Evidence from various studies suggests that IESCs repair the gut and reduce intestinal permeability
.
After a stroke, these repair processes may be essential for
maintaining cognitive function.
"It's clear that the brain-gut axis is associated with damage after stroke," said Dr.
Farida Sohrabji, managing professor and chair of the Department of Neuroscience and Experimental Therapeutics, and senior author
of the study.
"Considering the impact of gut health on the brain after a stroke allows us to advance stroke treatment
more effectively.
"

With this in mind, Sohrabji and her team transplanted primary IESCs from healthy donors after stroke in a preclinical model
.
IESCs from young donors repair intestinal structures and reduce intestinal permeability, which lowers levels of proteins and other molecules in the blood that are toxic to brain cells
.
IESC transplantation also prevents depressive-like behavior and cognitive impairment
in the weeks following stroke.
IESC transplantation of older donors did not improve stroke prognosis, suggesting that successful transplantation depends on the age
of the donor.

This study, which is still in the preclinical phase, highlights the importance of early therapeutic interventions after stroke and will guide future work directions
.
"Future studies will investigate the dosage and timing
of improving the protocol," Sohrabji said.
"Systematic studies of senescent stem cells are also important
to explain why older patients experience more severe strokes.
"

Neuroscientist Sohrabji, who has made a significant contribution to the literature on stroke pathogenesis, explained that the preclinical study was spearheaded by Dr.
Kathiresh Kumar Mani, an associate research scientist in her lab
.
Mani trained in gut biology and received a postdoctoral grant from the American Heart Association to support the project
.
Combined with their expertise, they have brought stroke treatment research into a new field with exciting results
.
They also received generous grants from the WoodNext Foundation to promote their innovative research
.

"Ultimately, this research is expected to lead to the development of new therapies that target and repair intestinal epithelial cells to help alleviate stroke disabilities," Sohrabji said, "but only if — intestinal stem cells may have therapeutic value outside the gut — can be considered for a wider variety of neurological diseases
.
" ”