Permeability change and brain tissue damage after intracarotid administration of cisplatin studied by double-tracer autoradiography in rats.
The present study was designed to find the reliable parameter(s) for the detection of early neurotoxicity following intracarotid (IC) administration of cisplatin. IC administration was performed for 60 minutes in female Wistar rats derived into four groups according to the dose given (1 mg, 1.2 mg, and 1.5 mg of cisplatin, and normal saline in control rats). Blood-brain barrier (BBB) permeability and local cerebral blood flow (LCBF) were measured by a double-tracer autoradiography technique using 1-[14C]-alpha-aminoisobutyric acid (14C-AIB) and 4-[18F] fluoroantipyrine (18F-FAP), respectively. Blood chemistry and neuropathology were also examined. BBB permeability was increased only on the ipsilateral side. This increase was dose-dependent, preceded the brain necrosis, and was statistically significant in the hypothalamus (1.2 mg group), auditory cortex and caudoputamen (1.5 mg group). Renal dysfunction was often observed. The changes in the LCBF did not occur until brain necrosis was noticeable. These findings demonstrate that the increase in the BBB permeability provides a sensitive and reliable indication of an early toxicity to brain tissue following IC administration of cisplatin.
Sugimoto
S
S
Cone Laboratory Neurosurgical Research, Montreal Neurological Institute & McGill University, Quebec, Canada.
Yamamoto
Y L
YL
Nagahiro
S
S
Diksic
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001345:Autoradiography / Q000379:methods*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D002250:Carbon Radioisotopes; D002339:Carotid Arteries; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D005260:Female; D005462:Fluorine Radioisotopes; D007269:Injections, Intra-Arterial; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D002945:Cisplatin