Figure 5.

VEGFR2 and p38 Mediate the Brain Microvascular Permeability Response

(A) Transendothelial flux of 4 kDa dextran across confluent primary rat brain MVECs was increased in response to basal but not apical VEGF-E (50 ng/ml). PlGF-1 (50 ng/ml) did not affect flux.

(B) Application of VEGF-E but not PlGF-1 to the abluminal, extravascular space of single pial microvessels in vivo produced a dose-dependent increase of permeability to sulforhodamine B (580 Da). Intracarotid (i.e., luminal) bolus injection of PlGF-1 or VEGF-E did not affect permeability.

(C) Flux measurements in primary brain MVECs showed that pretreatment with 10 μM p38 inhibitor SB202190 (SB) but not the PI3K inhibitor wortmannin (WN) inhibited the permeability response to 50 ng/ml VEGF-A.

(D) VEGF-A-induced permeability changes in pial microvessels were abolished by pretreatment with 10 μM SB202190 but not wortmannin.

Shown are means ± SEM from at least three independent experiments. ^∗p < 0.05, ^∗∗p < 0.01; ns, not significant [Student’s t test (A), ANOVA and Dunnett’s post hoc test (B and D), and two-way ANOVA and Bonferroni’s post hoc test (C)].

See also Figure S4.