Cerebrovascular permeability changes during experimental meningitis in the rat.
Alterations in the blood-brain and blood-cerebrospinal fluid barriers occur during bacterial meningitis. Preventing barrier alterations is important as the increases in barrier permeability are thought to contribute to adverse neurological outcomes. The objective of this study was to characterize pharmacokinetically cerebrovascular permeability alterations during meningeal inflammation. 14C-Sucrose was used as a quantitative marker of cerebrovascular integrity 8 hr after induction of experimental meningitis by intracisternal injection of 0, 25 or 200 micrograms lipopolysaccharides. Serum and brain tissues were obtained after tracer dosing. 14C-Sucrose influx transfer coefficients (Kin(app)) and cerebrovascular volumes (Vbr) were calculated for each brain region. Regional Vbr values were unaffected by lipopolysaccharide pretreatment. However, statistically significant increases in 14C-sucrose K(in)(app) values were observed in various brain regions (1.6- to 3.3-fold from control; P < .05). These permeability alterations cannot be attributed to changes in the systemic pharmacokinetics of 14C-sucrose as total clearance and the volume of distribution were unaffected by lipopolysaccharide treatment. This approach can be used in future studies to examine the contribution of various inflammatory mediators to altered cerebrovascular permeabilities during experimental meningitis.
Boje
K M
KM
Department of Pharmaceutics, School of Pharmacy, University of Buffalo, New York, USA.
D000818:Animals; D001812:Blood-Brain Barrier; D002199:Capillary Permeability / Q000502:physiology; D002250:Carbon Radioisotopes; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008581:Meningitis / Q000378:metabolism / Q000503:physiopathology*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D008070:Lipopolysaccharides; D013395:Sucrose