Ischaemic brain tissue sends inflammatory signals to the brain and immune organs to initiate a local and systemic immune response. The gastrointestinal tract is an important immune organ, with its pool of immune cells accounting for more than 70% of the total immune system. As such, the gut responds early to stroke, due in part to stroke-triggered activation of the vagus nerve, in addition to inflammatory signals from the brain. Often, these interactions result in intestinal motility disorders, dysbiosis of the gut microbiota, hyperpermeability, intestinal bleeding and sometimes even sepsis originating in the gut, which is often associated with a poor prognosis.1 Impairment of the intestinal barrier allows toxic compounds to leak into the blood, exacerbating inflammation and brain damage.
Therefore, a better understanding of the inflammatory and immune response of the gut after stroke has been a focus over several years for the development of effective stroke therapies. A highly exciting study published in January 2023 by a leading team from Texas looks at a novel preclinical therapy for stroke using intestinal epithelial stem cells (IESCs).2
To do this, organoids with IESCs derived from young, healthy rats were transplanted into older rats with stroke, where they repaired the changes in the gut caused by the stroke. The transplantation reduced stroke-induced mortality, decreased the volume of dead brain tissue and gut hyperpermeability. The intervention also lowered circulating levels of the endotoxin LPS and the inflammatory cytokine IL-17A. Remarkably, the IESC grafts also improved stroke-induced acute sensory-motor disability and protected against stroke-induced cognitive decline and depressive symptoms in the first four weeks after the event. By contrast, IESCs from older donor rats showed senescent characteristics and were not therapeutic.
Strokes are the most common cause of permanent disability. The researchers hope that the approach will help to reduce the burden of disease in this area. The basic idea - that intestinal stem cells could also be useful outside the gut - could be relevant to many other neurological diseases.3