The Role of Intestinal Alkaline Phosphatase in Ischemic Stroke

Grace Maley*, Allison Brichacek and Candice Brown, Department of Neuroscience, School of Medicine, West Virginia University, Morgantown, WV 26505

Field (Broad Category): Neuroscience-Microbiology (Health Sciences) 

Student’s Major: Biochemistry 

Stroke is the fifth leading cause of death in the United States. Therapeutic drugs to treat stroke and improve post-stroke recovery are limited. Recent literature demonstrates that stroke results in both brain and systemic inflammation, although the mechanisms are complex and not well understood. Previously, our lab has found evidence for chronic gut dysbiosis following ischemic stroke. The gut-derived enzyme, intestinal alkaline phosphatase (IAP), regulates gut homeostasis by maintaining a tight gut barrier. Previous studies have found that when Akp3, the gene that codes for IAP, is deleted, systemic inflammation increases. We hypothesized that mice with Akp3 gene deletion (Akp3-/-) would exhibit more severe brain and gut inflammation compared to control mice when subjected to ischemic stroke. Akp3-/- and control mice were subjected to 60 minutes of stroke or placebo surgery followed by euthanasia after seven days. Brain and intestine tissues were harvested for analysis at the time of euthanasia. Changes in brain blood flow were examined before, during, and after surgery. Akp3-/- stroke mice showed a significant decrease in brain blood flow compared to control mice. Overall, Akp3-/- stroke mice had decreased survival rates compared to control stroke mice with no significant differences in clinical or behavioral scores. Akp3-/- stroke mice also showed a significant increase in aerobic gut bacteria compared to control mice. In addition, fecal bacteria were also higher in Akp3-/- stroke mice. Taken together, these findings demonstrate that intestinal anti-inflammatory signals, such as those from IAP, are critical for stroke recovery in mammals. 

Funding: 

Program/mechanism supporting research/creative efforts: WVU's Research Apprenticeship Program (RAP) & accompanying HONR 297-level course