Blood-brain barrier disruption in immature Fischer 344 rats

Abstract

Methods for transiently disrupting the blood-brain barrier (BBB) which are consistent with survival are described for immature Fischer 344 rats weighing 40 to 99 gm. A catheter was retrogradely inserted into the external carotid artery to the level of the bifurcation. Perfusion of 1.4 M mannitol or 1.6 M arabinose, at a rate of 0.01 to 0.1 ml/sec for 30 seconds, resulted in transient BBB disruption as measured by Evans blue dye (EBD) staining. Higher flow rates or perfusion with 10% to 30% dimethyl sulfoxide were associated with a mortality rate ranging from 0% to 44%. Perfusion with 0.9% sodium chloride or intrafemoral artery perfusion with 1.4 M mannitol did not disrupt the BBB. Optimum BBB disruption as measured by EBD staining was achieved with 1.6 M arabinose at 0.026 ml/sec for 30 seconds, at which time all of the 42 experimental animals had BBB disruption; all of the animals so treated survived 2 weeks following perfusion. This technique will allow the efficacy of delivering chemotherapeutic agents following BBB disruption to be tested in several of the more commonly used small-animal models for brain-tumor research.