How gut repair saves brain function after stroke

Stroke is a leading cause of death, dementia and serious long-term disability. According to the American Heart Association, stroke patients also have a higher risk of depression, which negatively affects rehabilitation and cognition.

The only drug approved by the Food and Drug Administration (FDA) for the treatment of stroke, is a recombinant tissue plasminogen activator, which must be given within a specific time frame after stroke onset and with limited success. To improve stroke outcomes, scientists at Texas A&M University School of Medicine are pioneering research into the link between intestinal permeability or leakage caused by stroke and cognitive decline.

The Texas A&M team investigated the novel idea whether transplantation of intestinal epithelial stem cells (IESCs) from healthy donors could repair the intestinal barrier after stroke and improve stroke outcomes. Results from them preclinical researchpublished in a magazine Brain, Behavior and Immunityshowed that IESC transplantation reduced stroke mortality, decreased dead tissue volume and intestinal leakage, and prevented stroke-induced cognitive decline.

two thirds of stroke patient According to a recent study, cognitive impairment will develop, while a third of stroke patients will go on to develop dementia, so more effective stroke therapies are needed. to preserve cognitive function after acute stroke and maintain protection for several weeks. next.

Although stroke treatment research has traditionally focused on the brain, the gut responds early and rapidly to stroke with changes that can precede many of the inflammatory events associated with stroke disease. These changes in the intestine, such as increased permeability, can lead to the movement of products synthesized in the intestine into the blood stream. Many of these products are toxic and therefore have the potential to increase inflammation and exacerbate brain injury from a stroke.

Evidence from many studies demonstrates that IESC repairs the intestines and reduces intestinal permeability. After a stroke, these repair processes can be crucial to maintaining cognitive function.

“It is clear that the gut-brain axis is involved in post-stroke trauma,” said Farida Sohrabji, PhD, Professor Regents, chair of the Department of Neuroscience and Experimental Therapeutics and lead author of the study. “Taking into account the effect of gut health on the brain after a stroke could allow us to develop more effective stroke therapies.”

With that in mind, Sohrabji and her team transplanted primary IESCs from healthy donors after stroke in a preclinical model. IESCs from young donors repaired intestinal structure and reduced intestinal permeability and thus reduced blood levels of proteins and other molecules that are toxic to brain cells.

The IESC implant also prevented depressive-like behaviors and cognitive decline in the weeks following a stroke. IESC transplantation from older donors did not improve stroke outcomes, suggesting that transplant success depends on the age of the donor.

Still at the preclinical stage, this study highlights the importance of early intervention after stroke and will guide future research directions. “Future studies will investigate fine-tuning the dosage and timing of the protocol,” Sohrabji said. “A systematic study of aging stem cells will also be important to explain why older patients have more severe strokes.”

Sohrabji, a neuroscientist who has made important contributions to the literature on stroke pathogenesis, explains that this preclinical study was conducted by Dr. Kathiresh Kumar Mani, a research scientist in the laboratory hers, leading.

“Ultimately, this study is expected to advance the development of novel therapies that target and repair the intestinal epithelium to help minimize The hit “But the premise — that intestinal stem cells may have therapeutic value outside the gut — could be considered for a wider variety of neurological diseases,” Sohrabji said.