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1988, Volume 75, Issue 6, pp 557-565

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

T. -E. O. Sokrab,
B. B. Johansson,
H. Kalimo,
Y. Olsson

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.

Role of veins and cerebral venous pressure in disruption of the blood-brain barrier.

W G Mayhan and
D D Heistad


Abstract

The goal of this study was to determine whether increases in cerebral venous pressure contribute to, and may account for, disruption of the blood-brain barrier during acute hypertension and hyperosmolar stimuli. We studied the relation between pial venous pressure and disruption of the blood-brain barrier during acute arterial hypertension, superior venae cavae occlusion, and superfusion with hyperosmolar arabinose. Sprague-Dawley rats were studied using intravital fluorescent microscopy and fluorescein-labelled dextran (mol. wt. = 70,000). Disruption of the blood-brain barrier was characterized by the appearance of microvascular leaky sites and quantitated by the clearance of fluorescein dextran. We measured pressure (servo null) in pial arterioles and venules 40-60 micron in diameter. Acute hypertension, occlusion of the superior venae cavae, and hyperosmolar arabinose produced leaky sites primarily in venules. Acute hypertension increased arteriolar pressure and also venular pressure, from 7 +/- 1 (mean +/- SE) to 28 +/- 2 mm Hg. Clearance of fluorescein dextran increased from 0.03 +/- 0.01 to 2.90 +/- 0.40 ml/sec X 10(-6). Occlusion of the superior venae cavae increased pial venous pressure from 7 +/- 1 to 30 +/- 3 mm Hg, and clearance of fluorescein dextran, from 0.02 +/- 0.01 to 3.10 +/- 0.59 ml/sec X 10(-6). In contrast to acute hypertension, there was a decrease in arterial and pial arteriolar pressure during occlusion of the superior venae cavae. Thus, similar increases in venous pressure during acute hypertension and superior venae cavae occlusion, despite directionally opposite changes in arterial and arteriolar pressure, produced similar disruption of the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Whole blood viscosity in MS females was higher than controls at 3 of 4 shear rates (p < 0.001) but in MS males blood viscosity was higher only at shear rate of 1.0 s−1 (p<0.05). MS erythrocyte filtration rates were significantly lower than controls (p<0.001). Leucocyte counts in MS were greater than controls both in males (p <0.01) and females (p < 0.001). MS erythrocyte morphology was greatly different from controls (p<0.0001) and erythrocyte membranes contained less sphingomyelin than controls (p<0.01) but more phosphatidylinositol plus phosphatidylserine (p<0.02).

We conclude that, because our findings indicate an identifiable and potentially correctable abnormality, it is possible to envisage an inhibition of the progressive nature of MS, with the hope of a better prognosis for patients.

the blood viscosity can become as great as 10 times that of water, and its flow through blood vessels is greatly retarded because of increased resistance to flow.[5] This will lead to decreased oxygen delivery.[6] Other factors influencing blood viscosity include temperature, where an increase in temperature results in a decrease in viscosity.