Effects of injection mechanics, pH of infusate and 6-hydroxydopamine on cerebromicrovascular permeability in rats

Abstract

The effects of altering the rate, manner and vehicle used for intracerebral injection upon microvascular permeability were studied in Sprague-Dawley rats employing horseradish peroxidase histochemistry. The volume of vehicle delivered and the site of intracerebral injection were kept constant. In comparison to continuous infusion, vascular permeability was significantly greater following manual (intermittent) injections; however, no differences were found when the infusion rate was decreased 10-fold. Use of a buffered vehicle (Hanks' balanced salt solution) with pH adjusted to 7.4, in contrast to the more commonly used non-buffered vehicle (saline-ascorbate), resulted in significant reductions in permeability. The apparent influence of the agent 6-hydroxydopamine (6-OHDA) on changes in vascular permeability was found to vary depending on the type and pH of the vehicle used for injection. Significantly greater permeability resulted with saline-ascorbate (pH 3.1) as the vehicle when compared to Hanks' balanced salt solution (pH 7.4). Changes in vascular permeability can therefore be produced by varying mechanical and vehicular factors which, in the case of 6-OHDA, far outweigh previously reported permeability changes specifically attributed to this neurotoxin.