Fumitada Hazama

Scanning electron microscopic study of endothelial cells of cerebral arteries from spontaneously hypertensive rats.

Endothelial cells of the cerebral arterial system in spontaneously hypertensive rats were investigated by scanning electronmicroscopy and found to show progressive changes such as increased microvilli, numerous plasmalemmal pits, enlargement of the cells and well-developed marginal folds. Regressive changes, such as balloon-like protrusions and crater-like cave-ins, were also observed. Platelet adhesion to the injured endothelial surface of cerebral arteries was frequent. The significance of these changes in the development of hypertensive cerebrovascular lesions is discussed.

Early changes of experimentally induced cerebral aneurysms in rats: scanning electron microscopic study.

To obtain information about the early changes of experimentally induced cerebral aneurysms in rats, the luminal surface of branching areas of their cerebral arteries was examined with a scanning electron microscope. At the branching sites of major cerebral arteries in the control animals, the intima just distal to the apex markedly protruded into the lumen forming a linear bank-like intimal pad. Along and distal to this pad, there was a shallow long groove (juxta-apical groove). Such grooves were much deeper and wider in experimental animals than those in the control rats. By studying various stages of early aneurysmal changes, cerebral aneurysms were proven to develop from such grooves. In deep juxta-apical grooves and small aneurysms, round regenerated endothelial cells with a large number of microvilli were diffusely present. Degenerated cells with balloons and craters were observed intermingled with such regenerated cells. Interendothelial gaps were also seen. The present study showed the complex structure of the apex of arterial bifurcation in rats, including bank-like intimal pads. Such complex structures of the branching sites were considered to be responsible for the initiation of cerebral aneurysms due to endothelial injury possibly caused by turbulent flow there.

NEURAL INVOLVEMENT IN KAWASAKI DISEASE

Neurological findings and histopathology of the nervous system were studied in 30 patients with Kawasaki disease.

Involvement of internal elastic lamina in development of induced cerebral aneurysms in rats.

To elucidate the role of the internal elastic lamina in the development of cerebral aneurysm, the bifurcation of the anterior cerebral artery and olfactory artery was histologically studied in control and experimental rats treated with unilateral carotid ligation and renal hypertension. Various stages of aneurysm formation were compared, and it was found that early aneurysmal changes were always present just distal to the apical intimal pad on the anterior cerebral artery side. The internal elastic lamina was thinned and fragmented just distal to the pad even in the very early stage of aneurysm formation when the medial layer was still present. In control rats, the internal elastic lamina had a tendency to thin and fragment at the site where aneurysms would develop in experimental rats. Our study shows that changes of the internal elastic lamina were present just distal to the pad even in control rats, which never develop cerebral aneurysms. Under hemodynamic stress augmented by experimental treatments, further degenerative changes of the internal elastic lamina and involvement of the medial layer are considered to occur and result in aneurysm formation there.

SIX CASES OF RARE MALIGNANT TUMORS OF THE LIVER

Akitsugu OJIMA, Taketoshi SUGIYAMA, Toshio TAKEDA, Fumitada HAZAMA, Kazuya NAKAKUKI, * Yuji UESUGI, Akio MIYAZAKI, Yasuyuki SUZUKI and Masakazu FUKUSHIMA Department of Pathology, Faculty of Medicine, Kyoto University Six cases of rare malignant tumors originating in the liver, mesenchyma1 and epithelial, encountered in our department during the past five yeilrs and the incidence in Japan are briefly reported in this paper.

CHANGES IN VASCULAR PERMEABILITY IN THE BRAIN OF STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS STUDIED WITH PEROXIDASE AS A TRACER

Cerebrovascular permeability in stroke‐prone spontaneously hypertensive rats (SHR) at various ages was histologically studied using horseradish peroxidase as a tracer and such was related to the cerebrovascular lesions in the animals. An increase in permeability was demonstrated in the brain of SHR, particularly in those animals with an extremely high blood pressure. Increased cerebrovascular permeability occurred in some animals without any organic vascular change or severe parenchymal changes, although edema was present. Histologically, the SHR brain with an increase in permeability showed mild focal edema, rarefaction of tissue and necrosis with cyst formation. Thus a transitional progress was evident. Localization of the increase in permeability corresponded well with the predilection sites of cerebrovascular lesions in SHR. Constrictions and dilatations of intracerebral arterioles and small arteries were also demonstrated by the peroxidase method, and the dilated arterial walls did reveal a darker staining. From these results it is strongly suggested that certain cerebrovascular lesions, especially necrosis with cyst formation in SHR are sequelae of the increased cerebrovascular permeability caused by a chronic hypertensive state.

Elastic skeleton of intracranial cerebral aneurysms in rats.

In an attempt to clarify the developmental mechanism of cerebral aneurysms, we studied the elastic skeleton of experimentally induced cerebral aneurysms in rats under scanning electron microscopy after hot formic acid extraction followed by freeze-drying. We produced cerebral aneurysms in 19 rats by unilaterally ligating the common carotid artery, inducing renal hypertension, and feeding beta-aminopropionitrile fumarate. The first noted change was the loss of folds protruding from the internal elastic lamina. Morphologic changes of the internal elastic lamina, considered to be primarily responsible for aneurysmal formation, occurred after the loss or disintegration of the elastic skeleton of first the intima, then the media. In large aneurysms with thick domes, we found proliferation of elastic lamellae that may reduce the risk of rupture. It seems probable that the complex elastic skeleton of the arterial wall may account for the mechanical properties of the artery and that growth of an aneurysm occurs due to disintegration of the elastic skeleton and not simply to rupture of the internal elastic lamina. We believe that such changes in the elastic skeleton are a property of the functional state of the cells that produce elastin.

Histopathological study of induced cerebral aneurysms in primates

Experimental cerebral aneurysms in monkeys induced by treating them with unilateral carotid ligation, renal hypertension, and beta-aminopropionitrile feeding were studied macroscopically and with light microscopy. Macroscopically, 13 cerebral aneurysms were observed in six of seven monkeys. Microscopically, the elastic lamina and the media ended around the beginning of the aneurysms. The thin aneurysmal walls consisted of fibrous connective tissues. All findings were generally in accordance with spontaneous lesions in humans. The induced cerebral aneurysms in primates are thought to be a suitable experimental model to clarify the pathogenesis of the disease.

Study of the elastic skeleton of intracranial arteries in animal and human vessels by scanning electron microscopy.

We studied the elastic skeleton of major cerebral arteries in rats, monkeys, and one human using scanning electron microscopy after hot formic acid extraction followed by freeze-drying. For comparison, we also examined the thoracic aorta and femoral artery of rats. The cerebral arteries of rats had one distinct internal elastic lamina connected to the thin adventitia with sponge-like medial elastic tissue. This internal elastic lamina had fenestrations, which we found to be less frequent in cerebral arteries than in extracranial arteries, and fold-like protrusions into the lumen. This finding has not been recognized before. Such protrusions were more prominent in cerebral arteries than in extracerebral arteries. At the apical intimal pad, the internal elastic lamina appeared to be continuous, making a honeycomb-like structure. The folds and fenestrations were numerous at the apex. There were no essential differences among species. Our study shows that the internal elastic lamina is not a simple sheet but part of the complicated architecture of the elastic tissue of the vessel wall. These differences in the elastic skeleton, including fenestrations and fold-like structures, in various sites of different arteries may explain the development of various localized vascular diseases.

Autoradiographic Investigation of Cell Proliferation in the Brain of Spontaneously Hypertensive Rats

SummaryCell proliferation in the brain of spontaneously hypertensive rats (SHR) and control Wistar rats of various ages was autoradiographically investigated using [3H]thymidine. The brain of SHR showed an increase in labeled cells. The increase of labeled cells was seen in the early stage of the development of hypertension when there were still no definite morphological changes in the cerebral vessel walls or brain parenchyma. The labeled cells tended to increase in number with the age of the animals. The distribution of these cells corresponded with areas of increased vascular permeability and cerebrovascular lesions, that is, water-shed regions. The labeled cells consisted of endothelial and adventitial cells of the intracerebral arterioles and pial arteries as well as glial cells. Arachnoid cells, subarachnoid cells, medial smooth muscle cells of the pial arteries were also labeled, though less intensely. The significance of labeled endothelial cells in the development of cerebrovascular changes and sequential parenchymal changes is discussed.