Permeability of the developing and mature blood-brain barriers to theophylline in rats.
1. In the present study, the uptake of theophylline and L-glucose into the adult and neonatal rat brain has been investigated. Steady state cerebrospinal fluid (CSF) and brain concentrations of theophylline were reached within 1 h following a single intraperitoneal (i.p.) injection, whereas steady state CSF and brain concentrations of L-glucose were not approached until after 5 h. 2. Steady state brain:plasma and CSF:plasma concentration ratios for theophylline and L-glucose in neonatal rats were significantly higher than ratios in adult rats. Erythrocyte:plasma ratios for theophylline in neonatal rats were also significantly higher than ratios in adult rats. Steady state ratios for theophylline were significantly higher than those for L-glucose in both neonatal and adult rats. 3. Respiratory acidosis (pH 6.9-7.0) did not affect steady state CSF:plasma or brain:plasma ratios for theophylline in neonatal or adult rats. In contrast, steady state CSF:plasma and brain:plasma ratios for L-glucose were increased by respiratory acidosis. 4. The lower steady state CSF:plasma, brain:plasma and erythrocyte:plasma ratios for theophylline in adult rats are likely to be due to a higher concentration of plasma proteins in adult blood compared with neonates, with a greater retention of protein-bound (non-exchangeable) theophylline in adult blood, and are unlikely to be due to p-glycoprotein-mediated efflux of theophylline at the adult blood-brain barrier.
Habgood
M D
MD
Division of Anatomy and Physiology, University of Tasmania, Hobart, Australia. mark.habgood@utas.edu.au
Knott
G W
GW
Dziegielewska
K M
KM
Saunders
N R
NR
D000142:Acidosis, Respiratory / Q000097:blood / Q000134:cerebrospinal fluid; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000502:physiology*; D002199:Capillary Permeability / Q000502:physiology; D002478:Cells, Cultured; D003078:Colchicine / Q000378:metabolism; D004727:Endothelium / Q000166:cytology; D004912:Erythrocytes / Q000378:metabolism; D005947:Glucose / Q000134:cerebrospinal fluid / Q000378:metabolism; D006935:Hypercapnia / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D014665:Vasodilator Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
D014665:Vasodilator Agents; D013806:Theophylline; D005947:Glucose; D003078:Colchicine