title: Quantitative evaluation of blood-cerebrospinal fluid barrier permeability in the rat with experimental meningitis using magnetic resonance imaging.
abstract: Disruption of the blood-brain barrier (BBB) and/or the blood-cerebrospinal fluid barrier (BCSFB) is thought to be one of the major pathophysiological consequences of meningitis and contributes to the development of adverse neurological outcomes. In order to clarify this hypothesis further, we sequentially quantified the permeability of these barriers with magnetic resonance imaging (MRI) contrast enhancement using gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) in rats with various experimentally-induced meningitis. Meningeal inflammation was elicited by an intracisternal injection of interleukin (IL)-1beta, prostaglandin (PG) E(2), or lipopolysaccharide (LPS). Barrier permeability was calculated from the gadolinium-enhancement ratio (GER) in the subarachnoid space (SAS). The secretion of Gd-DTPA into the SAS was monitored by T1-weighted imaging after an intravenous injection of Gd-DTPA. As a significant linear correlation was observed between the GER and the standard solution, the concentration of the secreted Gd-DTPA were determined from the GER. The maximal intensity in SAS was detected at 5min after Gd-DTPA administration and it declined gradually. Among the inflammatory agents, IL-1beta was found to induce the most severe meningitis as determined from the GER. The concentration of Gd-DTPA in the SAS increased in a dose-dependent manner following IL-1beta intracisternal injection. On the other hand, no significant changes in signal intensity of the brain parenchymal areas due to IL-1beta injection were observed. The findings suggest that the permeability of the BCSFB can be evaluated quantitatively by calculating the GER. MRI with Gd-DTPA provides a useful method to monitor the change in the permeability to the brain barriers.
authors.affiliation: Third Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Tokushima 771-0192, Japan. hichikawa@research.otsuka.co.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Mari
authors.initials: M
authors.lastname: Fukunaga
authors.forename: Koichi
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ishiyama
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology*; D002199:Capillary Permeability; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D007089:Image Enhancement / Q000379:methods*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008581:Meningitis / Q000473:pathology*; D051381:Rats; D013346:Subarachnoid Space
chemical_list: D019786:Gadolinium DTPA