A quantitative evaluation of the permeability of the blood brain barrier of portacaval shunted rats.
The integrity of the blood-brain barrier (BBB) was measured in male Sprague Dawley rats subjected to 16 weeks of portacaval shunting (PCS), the optimal time required for the cerebral changes to develop, by using an in situ brain perfusion technique. The penetration of a vascular space marker 14C mannitol, and labelled amino acids 3H-phenylalanine or 3H-glutamate were measured in brain and cerebrospinal fluid (CSF) using an in situ brain perfusion technique, over 2 or 20 minutes. The patency of the surgical shunt was confirmed by measurement of significantly increased plasma ammonia (131.5 +/- 14.8 micromol x l(-1)) and AST (159.5 +/- 19.9 IU x l(-1)) concentrations compared to controls 39.9 +/- 3.7*, and 82.5 +/- 6.6* respectively. Brain and CSF 14C-mannitol space (ml x 100g(-1)), was not increased by PCS where brain space was 1.31 +/- 0.27 mL x 100g(-1) compared to control 1.19 +/- 0.49 mL x 100g(-1), and CSF was 0.14 +/- 0.06 mL x 100g(-1) compared to control 0.15 +/- 0.05 (PCS n=10, control n=8). The uptake for 3H-glutamate, which is required for cerebral ammonia detoxification, was also unchanged in both brain and CSF. However, brain uptake of 3H-phenylalanine was significantly reduced from 871 +/- 80 microL x min(-1) x g(-1) to 356 +/- 154* microl x min(-1) x g(-1) (n=4), although there was no change in CSF uptake. These data suggest that there is no generalized breakdown of the blood-brain or blood-CSF barriers during PCS as assessed by mannitol penetration. The reduction in phenylalanine uptake into the brain may help stabilize high cerebral aromatic amino acid levels. *P<0.05, Two-tailed, Student's unpaired t-test.
Alexander
B
B
Academic Department of Surgery, GKT School of Medicine & Dentistry, St Thomas' Hospital, London, UK. B.Alexander@kcl.ac.uk
Li
X
X
Benjamin
I S
IS
Segal
M B
MB
Sherwood
R
R
Preston
J E
JE
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002250:Carbon Radioisotopes; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D006501:Hepatic Encephalopathy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008353:Mannitol / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D010539:Permeability / Q000187:drug effects; D010649:Phenylalanine / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D011167:Portacaval Shunt, Surgical / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D000085:Acetates; D002250:Carbon Radioisotopes; D014316:Tritium; D018698:Glutamic Acid; D008353:Mannitol; D010649:Phenylalanine; C018824:ammonium acetate