Implantation of Brain-Derived Extracellular Matrix Enhances Neurological Recovery after Traumatic Brain Injury

Abstract

Scaffolds composed of extracellular matrix (ECM) are being investigated for their ability to facilitate brain tissue remodeling and repair following injury. The present study tested the hypothesis that the implantation of brain-derived ECM would attenuate experimental traumatic brain injury (TBI) and explored potential underlying mechanisms. TBI was induced in mice by a controlled cortical impact (CCI). ECM was isolated from normal porcine brain tissue by decellularization methods, prepared as a hydrogel, and injected into the ipsilesional corpus callosum and striatum 1 h after CCI. Lesion volume and neurological function were evaluated up to 35 d after TBI. Immunohistochemistry was performed to assess post-TBI white matter integrity, reactive astrogliosis, and microglial activation. We found that ECM treatment reduced lesion volume and improved neurobehavioral function. ECM-treated mice showed less post-TBI neurodegeneration in the hippocampus and less white matter injury than control, vehicle-treated mice. Furthermore, ECM ameliorated TBI-induced gliosis and microglial pro-inflammatory responses, thereby providing a favorable microenvironment for tissue repair. Our study indicates that brain ECM hydrogel implantation improved the brain microenvironment that facilitates post-TBI tissue recovery. Brain ECM offers excellent biocompatibility and holds potential as a therapeutic agent for TBI, alone or in combination with other treatments.