Infusible Extracellular Matrix Biomaterial Promotes Vascular Integrity and Modulates the Inflammatory Response in Acute Traumatic Brain Injury.

Traumatic brain injury (TBI) affects millions of people each year and in many cases results in long term disabilities. Once a TBI has occurred, there is significant breakdown of the blood-brain barrier resulting in increased vascular permeability and progression of the injury. In this study we investigated the use of an infusible extracellular matrix derived biomaterial (iECM) for its ability to reduce vascular permeability and modulate gene expression in the injured brain. First, we characterize the pharmacokinetics of iECM administration in a mouse model of TBI and demonstrate robust accumulation of iECM at the site of injury. Next, we show that iECM administration after injury can reduce the extravasation of molecules into the brain, and in vitro, iECM increases trans-endothelial electrical resistance (TEER) across a monolayer of TNFα-stimulated endothelial cells. In gene expression analysis of brain tissue, iECM induces changes that are indicative of downregulation of the pro-inflammatory response 1 day post-injury/treatment and neuroprotection at 5 days post-injury/treatment. Therefore, iECM shows potential as a treatment for TBI. This article is protected by copyright. All rights reserved.