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A transient hypertensive opening of the blood-brain barrier can lead to brain damage

Extravasation of serum proteins and cellular changes in rats subjected to aortic compression

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Summary

A transient increase in blood pressure was induced in 15 male Sprague Dawley rats by clamping the upper abdominal aorta for 8–10 min. Three rats served as controls. The brains were fixed by perfusion 2 h or 7 days later. Evan's blue-albumin (EBA) was used for macroscopic evaluation of the blood-brain barrier (BBB) integrity. Extravasated plasma albumin, fibrinogen and fibronectin were demonstrated by immunohistochemistry on paraffin sections. Glial fibrillary acidic protein (GFAP) was visualized in the same way. Parallel sections were analyzed for possible parenchymal changes associated with the BBB breakdown. Multiple focal areas of BBB opening were seen in the brains of the three rats killed 2 h after the hypertensive episode. The plasma proteins were present in the vascular wall, extracellular space and within certain neurons. Shrunken acid fuchsin positive neurons were seen in some areas of extravasation. After 7 days, in 5 out of 12 rats a few local lesions with EBA leakage and positive immunostaining for plasma proteins were seen. Structurally these lesions were characterized by shrinkage, fuchsinophilia and disintegration of neurons and proliferation of astrocytes. Thus, a transient opening of the BBB by acute hypertension may lead to permanent tissue damage.

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Supported by grants from the Swedish Medical Council, projects 14X-4698, 12X-03020 and 12X-07123, The Finnish Medical Research Council, The Swedish Multiple Sclerosis Society and The Rut and Erik Hardebo's Donation fund

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Sokrab, T.E.O., Johansson, B.B., Kalimo, H. et al. A transient hypertensive opening of the blood-brain barrier can lead to brain damage. Acta Neuropathol 75, 557–565 (1988). https://doi.org/10.1007/BF00686200

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