Stroke is a major cause of dementia, significant long-term damage, and death. According to the American Heart Association, stroke patients are more likely to develop depression, which has a negative impact on functional and cognitive recovery.
The Texas A&M researchers looked at whether transplanting intestinal epithelial stem cells (IESCs) from healthy donors may restore the intestinal barrier after stroke and enhance outcomes. According to the findings of their preclinical investigation, published in the journal Brain, Behavior, and Immunity, IESC transplantation reduced stroke-induced mortality, reduced the amount of dead tissue and gut leakiness, and averted stroke-induced cognitive impairment.
The only recombinant tissue plasminogen activator approved by the FDA for stroke therapy has a limited track record and must be taken shortly after the beginning of the stroke. Texas A&M University School of Medicine researchers are spearheading research into the association between stroke-induced intestinal permeability, or leakiness, and cognitive impairment, with the objective of improving stroke outcomes.
According to recent research, two-thirds of stroke patients will develop cognitive impairment, and one-third of all stroke patients will develop dementia, so there is a critical need for more effective stroke therapies that preserve cognitive function after acute stroke and remain protective in the weeks following.
Although most stroke therapy research is focused on the brain, the gut responds to stroke quickly and with alterations that may predict many of the inflammatory processes associated with stroke-induced illness. These alterations in the gut, such as increased permeability, are likely to result in the transfer of products generated in the gut into the bloodstream. Many of these products are hazardous, posing a risk of increasing inflammation and exacerbating stroke-induced brain damage.
IESCs heal the gut and decrease permeability, according to evidence from a range of research. These healing pathways may be crucial in retaining cognitive function after a stroke.
“It is clear that the gut-brain axis is involved in injury following stroke,” said Farida Sohrabji, PhD, Regents Professor, department head for Neuroscience and Experimental Therapeutics and senior author of the study. “Factoring in the effects of gut health on the brain following stroke may allow us to more effectively advance stroke therapies.”
In a preclinical model, Sohrabji and her colleagues implanted primary IESCs from healthy donors following stroke.
IESCs derived from young donors restored gut architecture and lowered gut permeability, lowering blood levels of proteins and other chemicals harmful to brain cells. In the weeks following the stroke, IESC transplantation also reduced depressive-like behaviours and cognitive impairment. IESC transplantation from older donors did not enhance stroke outcomes, demonstrating that donor age influences transplant success.
This research, which is still in the preclinical stage, emphasises the necessity of early treatment intervention after stroke and will influence future directions of the work. “Future trials will look towards refining the protocol’s dose and timing,” Sohrabji added. “A comprehensive study of ageing stem cells might also be useful in explaining why older people have more severe strokes.”
Sohrabji, a neurologist who has made major contributions to the literature on stroke causation, revealed that Kathiresh Kumar Mani, PhD, an associate research scientist in her lab, directed this preclinical work. The American Heart Association provided a postdoctoral grant to Mani, who is versed in gut biology, to assist this investigation.
Their combined knowledge has enabled them to take stroke treatment research into new area, with promising outcomes. They also won a large grant from the WoodNext Foundation, which is assisting them with their unique research.
“Ultimately, this research is expected to advance development of novel therapies that target and repair the intestinal epithelium to help mitigate stroke disability,” Sohrabji said, “but the premise–that gut stem cells might be therapeutically valuable outside of the gut–could be considered for a much greater variety of neurological diseases.”