Evaluation of Neurotoxicity and Radiation Effects of BNCT in Rats Following Blood-Brain Barrier Disruption and Intracarotid Injection of BPA or BSH

Abstract

The blood-brain barrier (BBB), which is formed by tight junctions of endothelial cells lining cerebral blood vessels and capillaries, effectively limits the delivery of most water soluble chemotherapeutic agents to brain tumors and surrounding brain tissue.1 Using the F98 rat glioma model, we recently have reported that osmotic blood-brain barrier disruption (BBB-D), produced by the intracarotid (i.c.) infusion of a hyperosmotic solution of mannitol, followed by i.c. administration of BPA or BSH significantly enhanced tumor boron delivery and the efficacy of BNCT in F98 glioma bearing rats.2–4 BPA and BSH have not been shown to have any significant short term neurotoxic and long term adverse radiation effects at doses that have been used clinically for BNCT.5,6 Since osmotic BBB-D transiently opens tight endothelial cell junctions of capillaries in both normal brain and tumor of the infused cerebral hemisphere,7 there is an increase in normal brain boron levels. However, by 2.5 hours these fall to values similar to those obtained following i.v. injection.2–4 The purpose of present study was to evaluate the short term neurotoxic and the long term neuropathologic and functional effects of BBB-D and i.c. infusion of BPA or BSH in non-tumor bearing rats following BNCT studies similar to those carried out in tumor bearing animals.2–4