Brain edema associated with severe chronic
hypertension was studied in
stroke-prone spontaneously hypertensive rats (SHRSP), 5 to 9 months of age. Blood-brain barrier (BBB) leakage sites and intracerebral spreading pathways for
plasma proteins were delineated by an intravenously (i.v.) injected exogenous
dye tracer (
Evans blue), known to form a complex with
albumin in blood, and by immunohistochemical visualization of extravasated endogenous
plasma proteins. The tissue content of
edema fluid was estimated by measuring the specific gravity of selected brain regions, stained or unstained by the tracer
dye, on a
bromobenzene-
kerosene gradient column. Multifocal BBB leakage sites were macroscopically detected within the cerebral cortex and the deep gray matter after i.v. circulation of
Evans blue-
albumin for 30 min. After 24 h of i.v. circulation the
dye tracer had spread not only locally in the gray matter but also into the adjacent white matter, where it was widely distributed. Immunohistochemically visualized
plasma proteins showed similar distribution. Unilateral superior cervical
ganglionectomy performed at 4 weeks of age neither increased the incidence of major BBB opening to
Evans blue-
albumin nor altered the specific gravity of the ipsilateral cerebral hemisphere in grown-up SHRSP, furthermore, the blood pressure remained unchanged. The lack of significant effect on BBB function may possibly be attributed to the extensive reinnervation of the cerebral arteries, verified in the grown-up SHRSP using the Falck-Hillarp fluorescence method for visualization of catecholaminergic nerve fibers. In SHRSP raised on a low-
protein and high-
salt diet the mean arterial blood pressure was 212 mm Hg compared to 195 mm Hg in controls (P less than 0.05) and the incidence of BBB opening was 72% compared to 25% in controls (P less than 0.05). After 24 h of i.v. circulation of
Evans blue-
albumin, brain regions stained by the
dye tracer showed significantly reduced specific gravity (P less than 0.001), while unstained regions had normal values. Thus the
brain edema fluid spread, as revealed by specific gravity measurements, corresponded to the intracerebral distribution of extravasated
plasma proteins.