Intestinal Stem Cell Transplant May Protect Brain After Stroke

Researchers at Texas A&M University report that transplanting intestinal epithelial stem cells (IESCs) from healthy donors reduced mortality and cognitive impairment after stroke. The preclinical study was published recently in the journal Brain Behavior and Immunity and provides further evidence for a link between stroke and gut permeability.

Stroke is a leading cause of death, dementia and serious long-term disability. Two-thirds of stroke patients will develop cognitive impairment, while one-third of all stroke patients will go on to develop dementia. There is a critical need for more effective stroke therapies that preserve cognitive function after acute stroke and that remain protective in the weeks following.

Although conventional stroke treatment research 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 gut changes, such as increased permeability, likely result in the movement of products that are synthesized in the gut into the blood stream. Many of these products are toxic and therefore in a position to increase inflammation and exacerbate stroke-induced brain injury.

Evidence from a variety of studies demonstrates that IESCs repair the gut and reduce gut permeability. After a stroke, these repair processes may be critical to preserving cognitive function.

“It is clear that the gut-brain axis is involved in injury following stroke,” says Farida Sohrabji, PhD, Regents Professor, Texas A&M 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.”

Sohrabji and her team transplanted primary IESCs from healthy donors after stroke in a preclinical model. IESCs from young donors repaired gut architecture and decreased gut permeability and consequently decreasing blood levels of proteins and other molecules that are toxic to brain cells. IESC transplantation also prevented depressive-like behaviors and cognitive impairment in the weeks following the stroke. IESC transplantation from older donors did not improve stroke outcomes, indicating that successful transplantation depends on the age of the donor.

The work research highlights the importance of early therapeutic intervention after stroke and will guide future directions of the work. “Future studies will investigate refinement of the dosing and timing of the protocol,” Sohrabji says. “A systematic study of aging stem cells would also be important to explain why older patients experience more severe strokes.”

Sohrabji adds that the study’s premise—that gut stem cells might be therapeutically valuable outside of the gut—could be considered for a much greater variety of neurological diseases.