Kenshi Yoshida

Effect of diltiazem and thromboxane A2 synthetase inhibitor (OKY-046) on vessels following experimental subarachnoid hemorrhage

In order to examine the functional changes in the vascular smooth muscle, the effects of a thromboxane A2 synthetase inhibitor (OKY-046) and a calcium channel blocker (diltiazem) on vessels following subarachnoid hemorrhage, and the contractile activity of cerebral vessels with various vasoactive agents, were investigated by studying isometric tension recordings in rings of cat basilar artery. The maximum contractile activities of the vessels in response to noradrenalin and adrenaline during the course of subarachnoid hemorrhage were significantly less than those in the control group. On the other hand, the maximum contractile activity of the vessels in response to prostaglandin F2 alpha on the seventh day following subarachnoid hemorrhage was significantly augmented compared with that in the control group. A significant decline in the relaxation of responsiveness to diltiazem during the course of subarachnoid hemorrhage was observed compared with that of diltiazem in the control group. This responsiveness to vasoactive agents was not influenced by the application of OKY-046. The present study reveals functional changes in vascular smooth muscle exposed to subarachnoid hemorrhage in response to vasoactive agents and a calcium entry blocker. Thromboxane A2 may not be a significantly influential factor in the present results. It is suggested that cerebral vasospasm may well be related to functional changes of the arterial wall, which appear to be associated with derangement of the mechanisms of smooth muscle constriction and dilatation based on organic changes.

Early cerebral blood flow and vascular reactivity to acetazolamide in predicting the outcome after ruptured cerebral aneurysm

The sequential cerebral blood flow (CBF) and CBF response to acetazolamide (AZ; 1 g i.v.) within 4 days after initial subarachnoid hemorrhage (SAH) were monitored in 50 patients by stable xenon‐enhanced computed tomography (xenon CT). The mean global CBF of the subjects declined with the neurological grading (Hunt & Kosnik), and it was impossible to predict the occurrence of vasospasm from the value of the plain CBF at the acute phase of SAH. However, the CBF response to AZ at the acute phase of SAH among patients resulting in a poor outcome was significantly diminished compared to that among patients resulting in a good outcome. The usefulness of the CBF response to AZ in the acute phase of SAH is discussed.

Pleomorphic xanthoastrocytoma: Ultrastructural study and origin of the tumor

An origin for the tumor cells of a pleomorphic xanthoastrocytoma (PXA) in a 50‐year‐old female is proposed on the basis of electron microscopic findings. The tumor was located in the superficial supratentorial region. Cytoplasmic positivity for GFAP in both the spindle cells and most of the bizarre giant cells was revealed by immunostaining, indicating an astocytic origin of the tumor. The presence of relatively few organelles, abundant filaments and microtubules, as demonstrated by electron microscopy, also indicated characteristics of astrocytes. Ultrastructural examinations revealed the existence of basal laminas in the extracellular space surrounding the surface of the tumor cells and the presence of localized cytoplasmic densities associated with the plasma membrane adjacent to the basal lamina resembling hemidesmosomes. This suggests a close relationship between the basal lamina and astrocytes, such as that between astrocytes and the investing basal in the glia limitans. The structures strongly indicated a cell origin for PXA that was not from non‐specific astrocytes with secondary proliferation of meningeal fibroblasts, but from astrocytes in the glia limitans with investing basal lamina.

Effect of diltiazem on calcium deposition in cerebral vessels after experimental subarachnoid hemorrhage

Calcium channel blockers such as diltiazem are being explored as agents to reduce or prevent cerebral vasospasm following subarachnoid hemorrhage (SAH). Yet little is known concerning changes over time in the calcium ions in the arterial wall after subarachnoid hemorrhage even when calcium channel blockers are used. The results imply that the massive increase of calcium ions in the smooth muscle cells in the early stages of SAH may be related to morphological changes in the spastic vessels in the subacute stage of SAH and calcium ion blockers might be useful in reducing organic changes in the vessels by the inhibition of calcium overloading.

Fine structure of epithelioid cells in cerebral tuberculoma

The ultrastructure of epithelioid cells from a tuberculous granuloma in the cerebrum of a 26‐year‐old male was studied. Light microscopic examinations of the border zone of the brain tuberculoma constantly revealed epithelioid cells. Fine structural examinations demonstrated two main types (type 1 and type 2) of epithelioid cells. Both types of epithelioid cells contained similar large pale nuclei. The cell membrane had many finger‐like processes interdigitating with those of the adjacent cells. The type 1 cells were distinguished by the presence of abundant organellae such as lamellar rough endoplasmic reticulum and mitochondria making a dark tone of cytoplasm. The type 2 cells showed a pale cytoplasm containing a few Golgi complexes and associated variably shaped vesicles. Another finding of note in the type 2 cells was the presence of subplasmalemmal linear densities (SLD). The morphology of the type 1 epithelioid cells was reminiscent of that of plasma cells displaying a biosynthetic function. Type 2 epithelioid cells with SLD, however, appeared to have a reduced biosynthetic function and to have contributed to a persistence of the granuloma structure. Neither type revealed identifiable phagocytosed material, and evidence of pinocytosis was practically absent. The presence of morphologic features of transitional cells, intermediate between type 1 and type 2 cells, suggests that these cells are related. It appears likely that type 1 is an early form of type 2. This is supported by the fact that type 2 corresponded roughly to the type ‘B’, which is thought to be a terminal‐stage cell. Furthermore, dying cells exhibited the structure of type 2 rather than type 1 cells.

Sequential changes in cerebral blood flow in patients with hypertensive subcortical intracerebral hematoma.

高血圧性皮質下脳出血の14症例を対象として, 脳血流の変化を術前後および慢性期に測定し, 転帰や血腫量との関連を検討した.全14症例は, 発症4日以内に血腫除去が施行された.術前の脳血流量は, 血腫および非血腫側ともに血腫量の増大に対して負の相関を認めて, 減少していた.一方, acetazolamide負荷後の脳血流の増加率は, 血腫量との相関を認めなかった.術後および慢性期では, 脳血流は血腫および非血腫側ともに血腫量および転帰に拘わらず増加を認めた.以上, 脳血流の面から, 高血圧性皮質下脳出血の治療を検討した.

Calcium ions and morphological changes in the arterial wall after subarachnoid hemorrhage, with special reference to human subjects

In order to clarify the relationship between calcium mobilization and morphological changes in the arterial wall after subarachnoid hemorrhage, electron microscopic histochemical assessments of the intracellular calcium in the arterial wall of human subjects showing vasospasm angiographically were conducted. Intracellular calcium ions in the arterial wall after subarachnoid hemorrhage were significantly more numerous than those of the control specimens. However, reaction products of calcium ions in the arterial wall were distributed mainly in the areas which morphologically revealed spastic changes such as myonecrosis and vacuoles, and there were no or extremely few reaction products of calcium ions in the areas showing no morphological changes in the arterial wall. These findings were consistent with the data for a feline model with experimental subarachnoid hemorrhage previously studied by the authors and indicated that increased intracellular calcium mobilization detected histochemically might be related to the morphological changes in the arterial wall after subarachnoid hemorrhage.

Giant cells in tumors associated with tuberous sclerosis

Electron microscopic studies of giant cells which appeared in tumors associated with tuberous sclerosis revealed an abundance of cytoplasm with large numbers of organelles and intermediate filaments, but not neurotubules or synaptic complexes. Furthermore, the presence of cilia, microvilli, formations of microrosette-like structures and complicated interdigitation of the folded processes of adjacent cells were confirmed. Immunohistochemical investigations of the cells showed positive reactions against GFAP-antiserum. It was concluded that the giant cells were of glial origin, predominantly having a potential to differentiate to ependymal cells.

Topographic Peculiarity in Spastic Changes of the Cerebral Artery After Subarachnoid Hemorrhage

Clinical observations have suggested that delayed ischemic neurological deficit caused by cerebral vasospasm is not always correlated with the location of spasm as revealed by angiography. Recent investigations have indicated an important role for arachidonic acid metabolites, especially prostacycline and thromboxane A2, in the genesis of cerebral vasospasm following subarachnoid hemorrhage [7, 10].