Permeability change and brain tissue damage after intracarotid administration of cisplatin studied by double-tracer autoradiography in rats

• Published in: Journal of neuro-oncology Vol. 24; no. 3; pp. 229 - 240
• Main Authors: SUGIMOTO, S, YAMAMOTO, Y. L, NAGAHIRO, S, DIKSIC, M
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01-01-1995
• Subjects: Animals; Antineoplastic Agents - toxicity; Autoradiography - methods; Biological and medical sciences; Blood-Brain Barrier - drug effects; Brain - drug effects; Carbon Radioisotopes; Carotid Arteries; Cerebrovascular Circulation - drug effects; Cisplatin - toxicity; Drug toxicity and drugs side effects treatment; Female; Fluorine Radioisotopes; Injections, Intra-Arterial; Medical sciences; Microcirculation - drug effects; Pharmacology. Drug treatments; Rats; Rats, Wistar; Toxicity: nervous system and muscle; Intracranial; Nervous system diseases; Cell permeability; Rat; Toxicity; Rodentia; Malignant tumor; Blood brain barrier; Cerebral disorder; Vertebrata; Chemotherapy; Mammalia; Treatment; Analysis; Animal; Carotid; Central nervous system disease; Tumor; Intraarterial administration
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/bf01052839

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.