Summary
The cerebrovascular lesions of severe chronic hypertension were studied by light microscopy in perfusion-fixed, subserially sectioned brains from stroke-prone spontaneously hyptertensive rats (SHRSP). The leakage and spread of plasma proteins were visualized by immunohistochemical detection of extravasated fibrinogen and by using an exogenous marker (Evans blue injected i.v.) for blood-brain barrier (BBB) dysfunction.
In most SHRSP the hypertension did not lead to major BBB lesions in spite of a mean arterial pressure around 200 mm Hg at 6–9 months of age. Multifocal BBB damage occurred in a minor group of SHRSP, particularly within the cortex and the deep gray matter. A close spatial correlation was found between the leakage-spread of plasma constituents and the neuropathologic alterations.
Fibrinoid degeneration of penetrating arterioles was found within the leakage sites. The surrounding gray matter showed petechial hemorrhages and abundant proteinaceous exudates rich in antifibrinogen-positive material. The current leakage of Evans blue and wide spread of fibrinoid substances suggested long-lasting damage to the BBB.
Most neurons within the edematous gray matter had well preserved nuclei surrounded by a rim of cytoplasm with ill-defined outline as if vacuolation or lysis of the peripheral cytoplasm had occurred. The sponginess of the tissue progressed in severe cases to formation of necrotic cysts. Condensed acidophilic neurons were seen in the border zone between the edematous and more compact gray matter. The appearance and distribution of the gray matter lesions deviated in many respects from those commonly seen in regional ischemic infarcts. The fibrin thrombi found close to the cysts might be regarded as secondary events.
The extensive spread of antifibrinogen-positive material within the white matter seemed to originate mainly from the chronic leakage sites in the gray matter. Increased number of large astrocytes were seen within the leakage sites and along the spreading pathways for the edema constituents. The white matter showed a rarefied texture with widely dispersed nerve fiber tracts, volume expansion, and occasional cyst formation.
The results indicate a crucial pathophysiologic role for the egress, spread, and accumulation of vasogenic edema in the development of the cerebrovascular lesions in SHRSP.
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Supported by the Swedish Medical Research Council (projects 12P-6827, 14X-4968, 12X-6238, 2X-07123, and 12X-03020), The Medical Faculty, University of Lund, The MS-Fund and Elsa Schmitz' Fund for Neurological and Neurosurgical Research
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Fredriksson, K., Auer, R.N., Kalimo, H. et al. Cerebrovascular lesions in stroke-prone spontaneously hypertensive rats. Acta Neuropathol 68, 284–294 (1985). https://doi.org/10.1007/BF00690831
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DOI: https://doi.org/10.1007/BF00690831