Effects of VEGF on the blood-brain barrier disruption caused by hyperosmolarity.
This study was performed to test whether disruption of the blood-brain barrier (BBB) caused by hyperosmolarity could be related to vascular endothelial growth factor (VEGF), using anti-VEGF antibody and ciclopirox olamine (CPX), an inducer of VEGF. CPX 50 mg/kg or normal saline was given intraperitoneally to male Wistar rats 18 h before BBB disruption. Two craniotomies were made on the ipsilateral cortex (IC-1 and IC-2) where the BBB would be disrupted, and a third hole was made on the contralateral cortex (CC) to expose the cortices. We applied normal saline (to IC-1 and the CC) or anti-VEGF antibody (to IC-2) for 90 min before BBB disruption with intracarotid injection of 25% mannitol. The degree of BBB disruption was determined by measuring the transfer coefficient (K(i)) of (14)C-alpha-aminoisobutyric acid and the volume of (3)H-dextran distribution. The protein levels of VEGF were determined with Western blot analysis. In the control animals, hyperosmolar mannitol significantly increased (415%) the K(i) in IC-1. The K(i) was attenuated with anti-VEGF antibody application (-28%, p < 0.05). Even though the protein levels of VEGF were strongly increased with CPX pretreatment, this upregulation did not alter the hyperosmolar BBB disruption in the saline- or in the antibody-treated cortex. The data on the volume of dextran distribution followed the same pattern as that of the K(i) but without a statistically significant difference between IC-1 and IC-2 in either group. Our data demonstrated that hyperosmolar BBB disruption could be attenuated with anti-VEGF antibody. However, upregulation of VEGF with CPX did not alter the degree of hyperosmolar BBB disruption with or without anti-VEGF antibody treatment. This study suggests that the contribution of VEGF in hyperosmolar BBB disruption is limited.
Chi
Oak Z
OZ
Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901-1977, USA. chi@umdnj.edu
Hunter
Christine
C
Liu
Xia
X
Tan
Tao
T
Weiss
Harvey R
HR
D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D015153:Blotting, Western; D000077768:Ciclopirox; D003399:Craniotomy; D003911:Dextrans / Q000493:pharmacokinetics; D004234:Diuretics, Osmotic; D008297:Male; D008353:Mannitol; D009994:Osmolar Concentration; D010296:Parietal Lobe / Q000378:metabolism; D011728:Pyridones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D000621:Aminoisobutyric Acids; D000906:Antibodies; D003911:Dextrans; D004234:Diuretics, Osmotic; D011728:Pyridones; D042461:Vascular Endothelial Growth Factor A; D000077768:Ciclopirox; C100049:2-aminoisobutyric acid; D008353:Mannitol