Cerebrovascular lesions in stroke-prone spontaneously hypertensive rats
- 90 Downloads
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.
Key wordsStroke-prone spontaneously hypertensive rats Blood-brain barrier Fibrinoid degeneration Brain edema
Unable to display preview. Download preview PDF.
- Adams RD, Vander Eecken HM (1953) Vascular diseases of the brain. Ann Rev Med 4:213–252Google Scholar
- Amano S (1976) Vascular changes in the brain of spontaneously hypertensive rats: hyaline and fibrinoid degeneration. J Pathol 121:119–128Google Scholar
- Auer RN, Wieloch T, Olsson Y, Siesjö BK (1984) The distribution of hypoglycemic brain damage. Acta Neuropathol (Berl) 64:177–191Google Scholar
- Bradbury M (1979) The concept of a blood-brain barrien. Wiley, New YorkGoogle Scholar
- Byrom FB (1954) The pathogenesis of hypertensive encephalopathy and its relation to the malignant phase of hypertension. Lancet II:201–211Google Scholar
- Chester EM, Agamanolis DP, Banker BQ, Victor M (1978) Hypertensive encephalopathy: a clinicopathological study of 20 cases. Neurology 28:928–939Google Scholar
- Chui E, Wilmes F, Sotelo JE, Horie R, Fujiwari K, Suzuki R, Klatzo I (1981) Immunocytochemical studies on extravasation of serum proteins in cerebrovascular disorders. In: Cervos-Navarro J, Fritschka E (eds) Cerebral microcirculation and metabolism. Raven Press, New York, pp 121–127Google Scholar
- Clemmensen J, Svendsen PJ (1973) Isolation of the plasmin resistant E-antigenic fibrinogen breakdown product by isotachophoresis. Sci Tools 20:5–6Google Scholar
- De Girolami U, Crowell RM, Marcoux FW (1984) Selective necrosis and total necrosis in focal ischemia. Neuropathologic observations on experimental middle cerebral artery occlusion in the macaque monkey. J Neuropathol Exp Neurol 43:57–71Google Scholar
- Dermietzel R, Eichner R (1979) Ultrastructure of cerebral capillaries in normotensive, spontaneously hypertensive, and acute hypertensive rats. Bibl Anat 18:174–176Google Scholar
- Ebhardt G, Mies G, Auer LM, Traupe H, Heiss W-D (1983) Neuronal injury following permanent middle cerebral artery occlusion in cats. Acta Neuropathol (Berl) 60:70–74Google Scholar
- Folkow B (1982) Physiological aspects of primary hypertension. Physiol Rev 62:347–504Google Scholar
- Giacomelli F, Wiener J, Spiro D (1970) The cellular pathology of experimental hypertension. V. Increased permeability of cerebral arterial vessels. Am J Pathol 59:133–159Google Scholar
- Hamilton PJ, Stalker AL, Douglas AS (1978) Disseminated intravascular coagulation: a review. J Clin Pathol 31: 609–619Google Scholar
- Hazama F, Amano S, Haebara H, Okamoto K (1975a) Changes in vascular permeability in the brain of stroke-prone spontaneously hypertensive rats studied with peroxidase as a tracer. Acta Pathol Jpn 25:565–574Google Scholar
- Hazama F, Ooshima A, Tanaka I, Tomimoto K, Okamoto K (1975b) Vascular lesions in the various substrains of spontaneously hypertensive rats and the effect of chronic salt ingestion. Jpn Circ J 39:7–21Google Scholar
- Johansson B (1980) The blood-brain barrier in acute and chronic hypertension. In: Eisenberg HM, Suddith RL (eds) The cerebral microvasculature. Plenum Press, New York, Adv Exp Med Biol 131:211–226Google Scholar
- Johansson B (1984) Cerebral vascular bed in hypertension and consequences for the brain. Hypertension 6:III81-III86Google Scholar
- Johansson B, Li C-L, Olsson Y, Klatzo I (1970) The effect of acute arterial hypertension on the blood-brain barrier to protein tracers. Acta Neuropathol (Berl) 16:117–124Google Scholar
- Johansson BB, Auer LM, Hodde KC, Nordborg C (1985) Cerebral resistance vessel morphometry in normotensive and hypertensive rats. In: Mulvany MJ, Strandgaard S, Hammersen F (eds) Resistance vessels. Physiology, pharmacology and hypertensive pathology. Karger, Basel. Progress in applied microcirculation 8:111–121Google Scholar
- Kalimo H (1976) The role of the blood-brain barrier in the perfusion fixation of the brain for electron microscopy. Histochem J 8:1–12Google Scholar
- Klatzo I, Wisniewski H, Steinvall O, Streicher E (1967) Dynamics of cold injury edema. In: Klatzo I, Seitelberger F (eds) Brain edema. Springer Verlag, Berlin Heidelberg, New York, pp 554–563Google Scholar
- Knox CA, Yates RD, Chen I-Li, Klara PM (1980) Effect of aging on the structural and permeability characteristics of cerebrovasculature in normotensive and hypertensive strains of rats. Acta Neuropathol (Berl) 51:1–13Google Scholar
- Majack RA, Bhalla RC (1981) Ultrastructural characteristics of endothelial permeability pathways in chronic hypertension. Hypertension 3:586–595Google Scholar
- Marmarou A, Nakamura T, Tanaka K, Hochwald GM (1984) The time course and distribution of water in the resolution phase of infusion edema. In: Go KG, Baethmann A (eds) Recent progress in the study and the therapy of brain edema. Plenum Press, New York, pp 37–44Google Scholar
- Nag S (1984) Cerebral changes in chronic hypertension: combined permeability and immunohistochemical studies. Acta Neuropathol (Berl) 62:178–184Google Scholar
- Nag S, Robertsson DM, Dinsdale HB (1980) Morphological changes in spontaneously hypertensive rats. Acta Neuropathol (Berl) 52:27–34Google Scholar
- Nordborg C, Johansson B (1980) A morphometric study on cerebral vessels in spontaneously hypertensive rats. Stroke 11:226–270Google Scholar
- Nordborg C, Fredriksson K, Johansson BB (1985) The morphometry of consectutive segments in cerebral arteries of normotensive and spontaneously hypertensive rats. Stroke 16:313–320Google Scholar
- Ogata J, Fujishima M, Tamaki K, Nakatomi Y, Ishitsuka T, Omae T (1980) Stroke-prone spontaneously hypertensive rats as an experimental model of malignant hypertension. Acta Neuropathol (Berl) 51:179–184Google Scholar
- Ogata J, Fujishima M, Tamaki K, Nakatomi Y, Ishitsuka T, Omae T (1981) Vascular changes underlying cerebral lesions in stroke-prone spontaneously hypertensive rats. Acta Neuropathol (Berl) 54:183–188Google Scholar
- Okamoto K, Yamori Y, Nagaoka A (1974) Establishment of the stroke-prone spontaneously hypertensive rat (SHR). Circ Res 34:143–153Google Scholar
- Onoyama K, Omae T (1973) Leakage of serum proteins in brain tissues in experimentally induced renal hypertension. Acta Neurol Scand 49:339–344Google Scholar
- Reulen HJ, Tsuyumu M (1981) Pathophysiology of formation and natural resolution of vasogenic brain edema. In: de Vlieger M, de Lange SA, Beks JWF (eds) Brain edema. Wiley, New York, pp 31–48Google Scholar
- Rosenberg EF (1940) The brain in malignant hypertension. Arch Int Med 65:545–586Google Scholar
- Sadoshima S, Heistad D (1982) Sympathetic nerves protect the blood-brain barrier in stroke-prone spontaneously hypertensive rats. Hypertension 4:904–907Google Scholar
- Shibota M, Shino A, Nagaoka A (1978) Cerebrovascular permeability in stroke-prone spontaneously hypertensive rats. Exp Molec Pathol 28:330–337Google Scholar
- Wiener J, Giacomelli F (1983) Hypertensive vascular disease. In: Genest J, Kuchel O, Hamet P, Cantin M (eds) Hypertension. Physiopathology and treatment, 2nd edn. MacGraw Hill, New York, pp 498–524Google Scholar
- Wolman M, Klatzo I, Chui E, Wilmes F, Nishimoto K, Fujiwara K, Spatz M (1981) Evaluation of the dye-protein tracers in pathophysiology of the blood-brain barrier. Acta Neuropathol (Berl) 54:55–61Google Scholar
- Yamori Y, Horie R, Sato M, Sasagawa S, Okamoto K (1975) Experimental studies on the pathogenesis and prophylaxis of stroke in stroke-prone spontaneously hypertensive rats (SHR). I. Quantitative estimation of cerebrovascular permeability. Jpn Circ J 39:611–615Google Scholar