A multiscale computational model of angiogenesis after traumatic brain injury, investigating the role location plays in volumetric recovery

Abstract

Vascular endothelial growth factor (VEGF) is a key protein involved in the process of angiogenesis. VEGF is of particular interest after a traumatic brain injury (TBI), as it re-establishes the cerebral vascular network in effort to allow for proper cerebral blood flow and thereby oxygenation of damaged brain tissue. For this reason, angiogenesis is critical in the progression and recovery of TBI patients in the days and weeks post injury. Although well established experimental work has led to advances in our understanding of TBI and the progression of angiogenisis, many constraints still exist with existing methods, especially when considering patient progression in the days following injury. To better understand the healing process on the proposed time scales, we develop a computational model that quickly simulates vessel growth and recovery by coupling VEGF and its interactions with its associated receptors to a physiologically inspired fractal model of the microvascular re-growth. We use this model to clarify the role that diffusivity, receptor kinetics and location of the TBI play in overall blood volume restoration in the weeks post injury and show that proper therapeutic angiogenesis, or vasculogenic therapies, could speed recovery of the patient as a function of the location of injury.

Keywords

• angiogenesis
• traumatic brain injury
• computational biology
• endothelial growth factor
• vegf
• cerebral vascular structure
• fractal branching
• vascular tree