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Ultrastructural observations on the transvascular route of protein removal in vasogenic brain edema

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Summary

Micro-blood vessels (MBVs), located in the area of edema, were studied in cat brain at various time intervals (1 h, 24 h, 7 days) after cold-lesion injury. Both cold-injured and adjacent gyri were examined for blood-brain barrier (BBB) permeability to i. v. injected horseradish peroxidase (HRP) with circulation times of 40 min and 24 h. Evans blue (EB) was used as a tracer for gross evaluation of the extension of brain edema. Localization of alkaline phosphatase (AP) and binding of cationized ferritin (CF), considered as a marker of anionic sites, were also studied ultrastructurally.

Twenty-four hours after cold injury, the extravasated edema fluid, outlined by EB tracer, was observed to be spreading through the white matter (WM) into the adjacent gyrus. At this time, numerous, larger than capillary MBVs, presumably arterioles and venules located in the edematous WM, showed accumulations of HRP injected at the time of the operation, in the basement membrane, in abluminal pits, and in numerous pinocytotic vesicles and vacuoles of endothelial cells (ECs).

The animals killed after 24 h with 40 min HRP circulation showed extravasation of HRP tracer in a zone underlying the necrotic cold injury lesion. On the other hand, there was no evidence of an abnormal HRP leakage in the further removed areas of edema in the WM, particularly in the adjacent gyrus.

These observations suggest that a reverse, vesicular transport of HRP across the ECs of some MBVs represents one of several possible mechanisms responsible for the removal of extravasated proteins and of edematous fluid from brain extracellular space. This reverse transport is accompanied by a disruption of the surface anionic layer and changed polarity of ECs manifested by the relocation of AP activity from luminal to abluminal plasmalemma.

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Supported in part by grant no. 17271-04 from the NINCDS

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Vorbrodt, A.W., Lossinsky, A.S., Wisniewski, H.M. et al. Ultrastructural observations on the transvascular route of protein removal in vasogenic brain edema. Acta Neuropathol 66, 265–273 (1985). https://doi.org/10.1007/BF00690958

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