Effects of VEGF on the blood-brain barrier disruption caused by hyperosmolarity

Oak Z. Chi, Christine Hunter, Xia Liu, Tao Tan, Harvey R. Weiss

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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 (Ki) of 14C-α-aminoisobutyric acid and the volume of 3H-dextran distribution. The protein levels of VEGF were determined with Western blot analysis. In the control animals, hyperosmolar mannitol significantly increased (415%) the Ki in IC-1. The Ki 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 Ki 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.

Original languageEnglish (US)
Pages (from-to)187-192
Number of pages6
JournalPharmacology
Volume82
Issue number3
DOIs
StatePublished - Oct 2008

All Science Journal Classification (ASJC) codes

  • Pharmacology

Keywords

  • Blood-brain barrier disruption
  • Ciclopirox olamine
  • Hyperosmolar solution
  • Vascular endothelial growth factor

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