The effect of a metabolic inhibitor upon the properties of the cerebral vasculature during a whole-head saline perfusion of the rat.

The effect of the metabolic inhibitor 2,4-dinitrophenol (DNP) has been assessed during a simple in situ Ringer solution perfusion of the rat brain. The preparation was perfused, with or without the addition of DNP, for periods ranging up to 30 min. Following this pre-test perfusion, both the vascular permeability and cerebral perfusate flow were assessed. In the absence of DNP significant barrier disruption had taken place by 10 min and the flow rates showed greater fluctuations with time. In the presence of DNP, however, perfusate flow remained constant and the blood-brain barrier remained intact to [14C]mannitol for at least 10 min, but subsequently the flow rate dropped and the barrier began to show evidence of disruption. The unbound visual marker, Evans Blue, was apparently excluded from all regions other than those that are known to lack a blood-brain barrier. The water content of the brain showed no significant increase until 20 min. Patency of the capillaries was demonstrated by direct visualization of the cerebral vasculature with an Indian ink-gelatin mixture and in some animals there was evidence of incomplete filling following 30 min of perfusion. It is concluded that the use of DNP in the perfusate provides a useful preparation for the short-term study of passive properties of the blood-brain barrier, such as carrier-facilitated diffusion, as well as mechanisms of barrier opening.