Fig. 8

Depletion of BAMs attenuates ischemia-induced pial and cortical vascular permeability. BAMs were depleted by i.c.v. administration of clodronate liposomes (CL) 4 days prior to ischemia. For treatment control, rats received vehicle liposomes (V). a) Vegfa mRNA was studied in cortical and subcortical regions of the ipsilateral (ipsi, ischemic) and the contralateral (contra) brain hemispheres. Ischemia-induced expression of Vegfa mRNA at 24 h is attenuated in the cortex of the CL rats versus the V rats (n = 6 per group) (Mann Whitney test, p = 0.041). b) Western blotting of cortical and subcortical brain tissue (ipsilateral) 24 h post-ischemia shows the VEGF₁₆₄ isoform of VEGF-A detected as two bands corresponding to the homodimeric and monomeric forms at approximately 54 kDa and 24 kDa. Quantification of signal intensity of the 54-kDa band shows reduced expression in the cortex of rats receiving CL vs. rats receiving V (n = 6 per group) (Mann-Whitney test, **p = 0.002). c) Ischemia increases the permeability of pial vessels (arrows), as assessed by Evans blue extravasation 24 h post-ischemia, and BAM depletion attenuates the effect. Images of one representative coronal brain section per rat of each treatment group show Evans blue extravasation in the ipsilateral hemisphere. Rats receiving clodronate show negligible Evans blue in the cortex (arrows in the schematic representation at the right hand side). The volume of tissue showing Evans blue extravasation is reduced in the cortex, but not in subcortical zones, of the CL group (n = 8) versus the V group (n = 7) (Mann-Whitney test, *p = 0.014)