Evaluation of Blood–Brain Barrier Disruption Using Low- and High-Molecular-Weight Complexes in a Single Brain Sample in a Rat Traumatic Brain Injury Model: Comparison to an Established Magnetic Resonance Imaging Technique

Traumatic brain injury (TBI), a major cause of death and disability among young people, leads to significant public health and economic challenges. Despite its frequency, treatment options remain largely unsuitable. However, examination of the blood-brain barrier (BBB) can assist with understanding the mechanisms and dynamics of brain dysfunction, which affects TBI sufferers secondarily to the injury. Here, we present a rat model of TBI focused on two standard BBB assessment markers, high- and low-molecular-weight complexes, in order to understand BBB disruption. In addition, we tested a new technique to evaluate BBB disruption on a single brain set, comparing the new technique with neuroimaging. A total of 100 Sprague-Dawley rats were separated into the following five groups: naive rats (<i>n</i> = 20 rats), control rats with administration (<i>n</i> = 20 rats), and TBI rats (<i>n</i> = 60 rats). Rats were assessed at different time points after the injury to measure BBB disruption using low- and high-molecular-weight complexes. Neurological severity score was evaluated at baseline and at 24 h following TBI. During the neurological exam after TBI, the rats were scanned with magnetic resonance imaging and euthanized for assessment of the BBB permeability. We found that the two markers displayed different examples of BBB disruption in the same set of brain tissues over the period of a week. Our innovative protocol for assessing BBB permeability using high- and low-molecular-weight complexes markers in a single brain set showed appropriate results. Additionally, we determined the lower limit of sensitivity, therefore demonstrating the accuracy of this method.