Investigating the role of the experimental protocol in phenylhydrazine-induced anemia on mice recovery

Abstract

Production of red blood cells involves growth-factor mediated regulation of erythroid progenitor apoptosis and self-renewal. During severe anemia, characterized by a strong fall of the hematocrit followed by a recovery phase, these controls allow a fast recovery of the hematocrit and survival of the organism. Using a mathematical model of stress erythropoiesis and an ad hoc numerical method, we investigate the respective roles of anemia-inducing phenylhydrazine injections and physiological regulation on the organism's recovery. By explicitly modeling the experimental protocol, we show that it mostly characterizes the fall of the hematocrit following the anemia and its severeness, while physiological process regulation mainly controls the recovery. We confront our model and our conclusions to similar experiments inducing anemia and show the model's ability to reproduce several protocols of phenylhydrazine-induced anemia. In particular, we establish a link between phenylhydrazine effect and the severeness of the anemia.

Keywords: Erythropoiesis model; Experimental protocol modeling; Nonlinear age-structured system.