Blood-spinal cord barrier disruption proximal to a spinal cord transection in the rat: time course and pathways associated with protein leakage.

The effects of spinal cord transection on the blood-spinal cord barrier of the rat were examined at the ultrastructural level at sites 0.5 and 1.0 cm proximal to the injury. Using the vascular tracer horseradish peroxidase (HRP), the time course and pathways of barrier disruption were evaluated. At 0.5 cm, barrier disruption was noted from as early as 15 min and continued to 12 h after injury, whereas at 1.0 cm, evidence for vascular permeability was confined to between 15 min and 3 h. The presence of barrier breakdown to exogenous protein at a distance from the transection emphasizes that injury promotes a more generalized vascular response which likely contributes to subsequent edematous changes. The mechanism(s) involved in increased permeability appears to be primarily related to transendothelial vesicular transport of the tracer. There was no evidence for interendothelial leakage of the tracer across compromised tight junctions. In comparing these findings with those reported on sites distal to a transection, it is clear that there is an asymmetry in the vascular response to HRP. The pinocytotic index, an indicator of endothelial uptake of HRP, was significantly elevated (compared with control) distal to a transection from 3 h through 3 days after injury, attaining a maximum at 12 h. In contrast, the pinocytotic index proximal to a transection was significantly elevated compared to control values at only 1 h after injury. Furthermore, at 3 h after injury, when barrier disruption was most prominent, there was a smaller percentage of vessels exhibiting leakage to HRP proximal as opposed to distal to a transection.