Recombinant Alkaline Phosphatase Administration Supports Gastrointestinal Barrier Function and Immune Response in Ischemic Stroke
Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B212
Abstract ID: 5415
Presenting Author:
Rhiannon V Macom
Abstract:
Emerging research supports the concept that strokes are systemic and stroke outcomes are influenced by the interactions between the brain and gastrointestinal (GI) tract, or gut-brain axis (GBA). Intestinal alkaline phosphatase (IAP) is a brush border enzyme in the intestinal endothelium that regulates intestinal homeostasis by reducing inflammation and maintaining barrier integrity. Recombinant alkaline phosphatase (recAP, AM-Pharma) has been shown reduce mortality in a subset of sepsis patients. We hypothesized that the loss of IAP will disrupt the GBA post-stroke and treatment with recAP will decrease post-stroke GI dysfunction. We used eight-month-old mice with a genomic deletion of Akp3, the gene that encodes IAP, and Akp+/+ littermate controls. Ischemic stroke was induced by cortical photothrombosis followed by recAP or saline vehicle administration at two-hours post-stroke followed by daily injections for 3 days. Result show that recAP treatment decreased cortical infarct volume and reduced intestinal bacterial burden. Flow cytometry showed that recAP decreased CD4+ (p=0.03) and CD11c+ (p=0.02) T-cell infiltration into the brain but did not alter any immune populations in the spleen. Ongoing analyses will evaluate recAP’s effects on intestinal barrier function by quantifying changes in gene expression and intestinal histology. These studies will provide important insights on the role of IAP in stroke and the therapeutic potential of recAP in stroke patients.
Recombinant Alkaline Phosphatase Administration Supports Gastrointestinal Barrier Function and Immune Response in Ischemic Stroke
Category
Poster and Podium (Block Symposium)