Changes in blood-brain barrier permeability associated with insertion of brain cannulas and microdialysis probes.
Blood-brain barrier (BBB) transcapillary transport was studied after insertion of cannulas and microdialysis probes into the brains of three groups of rats. Quantitative autoradiography was used to measure changes in BBB permeability around the insertion site. In the first group, BBB function was measured with 14C-sucrose at times from immediately, and up to 28 days, after insertion of a microdialysis probe. BBB function was disrupted biphasically: a 19-fold increase in the influx constant (K1) of sucrose occurred immediately after insertion with a second 17-fold increase at 2 days, followed by a slow decline to 5 times normal values at 28 days. In the second group, 14C-dextran (70 kDa) was used to measure BBB transcapillary transport; K1 was increased 90-fold after probe insertion. In the 3rd group, 14C-AIB (alpha-aminoisobutyric acid) was used to evaluate BBB transport after insertion of a 27 gauge cannula, which was used to infuse 1 microliter of saline over 5 min. The K1 of AIB was increased 25 times control values. We conclude that BBB transcapillary transport function is disturbed in response to insertion of brain cannulas and/or microdialysis probes, that BBB dysfunction is maximal at the cannula or probe tip, varies with time after insertion, may persist for at least 28 days after insertion, and occurs over a wide molecular range of solutes. These results suggest caution when using microdialysis as a method to study normal BBB function, and suggest that microdialysis may overestimate the rate of transfer into and out of the brain.
Groothuis
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DR
Department of Neurology, Northwestern University Medical School, Evanston Northwestern Healthcare, Evanston, IL 60201, USA. drgroothuis@nwu.edu
Ward
S
S
Schlageter
K E
KE
Itskovich
A C
AC
Schwerin
S C
SC
Allen
C V
CV
Dills
C
C
Levy
R M
RM
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002199:Capillary Permeability / Q000502:physiology*; D002404:Catheterization / Q000009:adverse effects* / Q000295:instrumentation; D007275:Injections, Intravenous; D008297:Male; D017551:Microdialysis / Q000009:adverse effects* / Q000295:instrumentation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism
D013395:Sucrose