Correlation between brain tissue and cerebrospinal fluid concentrations of selected compounds in rats with intact and injured blood-brain barrier.
We examined how the concentrations of exogenous compounds (and their metabolites) in rat brain tissue correlate with their concentrations in the cerebrospinal fluid (CSF) (i) when the blood-brain barrier (B-BB) is intact and increasing doses of compounds are administered, and (ii) when the function of the B-BB is impaired and small constant doses are given. The impairment of B-BB function was caused by chlorophenoxyacetic acid herbicides. An excellent linear correlation between brain tissue and CSF concentrations, calculated from 14C activities, was obtained with 14C-p-aminobenzoic acid, 14C-antipyrine, and 14C-sucrose administered in increasing doses (to 320 mg/kg, i.v.) to B-BB-intact animals (r = 0.92 to 0.99, P less than 0.001). After the administration of small, constant, i.v. doses of 14C-methyl-4-chlorophenoxyacetic acid, 14C-2,4-dichlorophenoxyacetic acid, or 14C-p-aminobenzoic acid into B-BB-damaged rats, both brain tissue and CSF radioactivities increased about linearly 10-fold or more when the lesions progressed. A close correlation between brain tissue and CSF radioactivities was calculated with each compound (r = 0.97 to 0.99, P less than 0.001). In tests with small constant amounts of 14C-antipyrine, 14C-sucrose, and 125I-labeled human albumin, however, no marked linear correlation could be drawn. This was due to the fact that these compounds always caused roughly the same 14C activities both in the brain tissue and in CSF, i.e., their cerebral penetration was only slightly or negligibly affected by the B-BB impairment. The results suggest that significant changes in compound penetration into rat brain tissue can be monitored in the CSF.
D000818:Animals; D001812:Blood-Brain Barrier; D001923:Brain Chemistry; D002555:Cerebrospinal Fluid / Q000032:analysis*; D002561:Cerebrovascular Disorders / Q000139:chemically induced / Q000378:metabolism*; D006540:Herbicides; D008297:Male; D051381:Rats / Q000378:metabolism*; D011919:Rats, Inbred Strains
D006540:Herbicides