Regional patterns of blood-brain barrier breakdown following central and lateral fluid percussion injury in rodents.

Abstract

In order to determine how fluid percussion injury (FPI) effect is distributed throughout the brain, and to assess the extent to which individual brain nuclei and regions are affected, the pattern of blood-brain barrier (BBB) breakdown was determined in groups with different injury cannula locations. Injury cannulas were placed either at midline, or 2 or 4 mm to the side. One hour following FPI, animals were given horseradish peroxidase (HRP) and the brains were stained using the TMB method. The distribution of HRP leakage varied considerably depending upon the location of the injury cannula, however, there were also common sites of leakage among these groups. Locally the cortex and hippocampus under and adjacent to the injury cannula were heavily affected, with a clear asymmetric effect in the lateral cannula groups. Common sites of leakage included the dorsal thalamus, septal area, pontine tegmentum, periaqueductal gray, substantia nigra, and narrow zones adjacent to ventricular or cisternal surfaces. The hippocampus tended to be involved at greater distances than the cerebral cortex. The cervicomedullary junction proved to be especially vulnerable to FPI with extensive HRP leakage, and petechial hemorrhage ranging from minor to fatal coalescent hemorrhage. A very narrow threshold separated these outcomes. Neurologic impairment of the animals correlated most directly with the extent of cervico-medullary junction injury. Thus FPI produces a mix of local and diffuse effects on the BBB. Injury at the cervicomedullary junction is a prominent effect and is the limiting factor in trying to establish more severe diffuse injury.