T cell function is dispensable for intracranial aneurysm formation and progression.

Given the social importance of intracranial aneurysm as a major cause of a lethal subarachnoid hemorrhage, clarification of mechanisms underlying the pathogenesis of this disease is essential for improving poor prognosis once after rupture. Previous histopathological analyses of human aneurysm walls have revealed the presence of T cells in lesions suggesting involvement of this type of cell in the pathogenesis. However, it remains unclear whether T cell actively participates in intracranial aneurysm progression. To examine whether T cell is involved in aneurysm progression, intracranial aneurysm model of rat was used. In this model, aneurysm is induced by increase in hemodynamic force loaded on bifurcation site of intracranial arteries where aneurysms are developed. Deficiency in T cells and pharmacological inhibition of T cell function were applied to this model. CD3-positive T cells were present in human aneurysm walls, whose number was significantly larger compared with that in control arterial walls. Deficiency in T cells in rats and pharmacological inhibition of T cell function by oral administration of Cyclosporine A both failed to affect intracranial aneurysm progression, degenerative changes of arterial walls and macrophage infiltration in lesions. Although T cells are detectable in intracranial aneurysm walls, their function is dispensable for macrophage-mediated inflammation and degenerative changes in arterial walls, which presumably leads to intracranial aneurysm progression.

E- and P-selectin are not required for the development of experimental autoimmune encephalomyelitis in C57BL/6 and SJL mice.

In multiple sclerosis and in its animal model experimental autoimmune encephalomyelitis (EAE), inflammatory cells migrate across the endothelial blood-brain barrier (BBB) and gain access to the CNS. It is well-established that alpha4 integrins are actively involved in leukocyte recruitment across the BBB during EAE. In contrast, the role of endothelial E- and P-selectin in this process has been a controversial issue. In this study, we demonstrate that P-selectin protein can be detected in meningeal blood vessel endothelial cells in healthy SJL and C57BL/6 mice and on rare parenchymal CNS blood vessels in C57BL/6, but not SJL, mice. During EAE, expression of P-selectin but not E-selectin was found up-regulated on inflamed CNS microvessels surrounded by inflammatory infiltrates irrespective of their meningeal or parenchymal localization with a more prominent immunostaining detected in C57BL/6 as compared with SJL mice. P-selectin immunostaining could be localized to CNS endothelial cells and to CD41-positive platelets adhering to the vessel wall. Despite the presence of P-selectin in wild-type mice, E/P-selectin-deficient SJL and C57BL/6 mice developed clinical EAE indistinguishable from wild-type mice. Absence of E- and P-selectin did neither influence the activation of myelin-specific T cells nor the composition of the cellular infiltrates in the CNS during EAE. Finally, endothelial-specific tetracycline-inducible expression of E-selectin at the BBB in transgenic C57BL/6 mice did not alter the development of EAE. Thus, E- and P-selectin are not required for leukocyte recruitment across the BBB and the development of EAE in C57BL/6 and in SJL mice.

A histological, ultrastructural and immunohistochemical study of superficial temporal arteries and middle meningeal arteries in moyamoya disease.

Pathologic changes in superficial temporal arteries (STA) and middle meningeal arteries (MMA) biopsied from 15 patients with moyamoya disease (MD) who had undergone cerebro-temporal arterio-synangiosis were studied histologically, ultrastructurally and immunohistochemically. The main pathologic features were: proliferation of smooth muscle cells (SMCs) and thickening of the intima, degeneration and destruction of SMCs in the media and intima, and the presence of condensed organelles in necrosed SMCs or the interstitium among SMCs, or both outside and within the elastica interna (EI). The EI had become thin, porous, fragmented and was even absent in some segments. These changes are different from those of other forms of angiopathy, but identical with those at the ends of internal carotid arteries (ICA) reported by us previously, being pathognomonic for MD. These changes in the STA and MMA reveal that MD involves not only the ICA but also the intra- and extracranial branches of external carotid arteries. The medial necrosis of SMCs seems to be the primary injury of the arterial wall in MD. STA tissue blocks from two cases of MD were stained immunohistochemically. By electron microscopy, IgG-, IgM-, and C3-positive granules were observed on the ER of endothelial and intimal cells. Further studies on more cases are needed to determine whether an immunoreaction has occurred in these arteries.