[Structural peculiarities of the wall of the vessels of the cerebral arterial circle in the area of bifurcations in people of different age].

The present study was conducted to determine the morphological and morphometric features of the arterial wall structure at the bifurcation of blood vessels of the cerebral arterial circle (CAC) of Willis in people of different age (from birth till 65 years). Material obtained from 80 people was stained with hematoxylin-eosin, Van Gieson stain, with orcein by Unna-Taenzer's method and with sudan. The proliferative activity of the cells in tunica intima and tunica media at the site of bifurcation of the internal carotid and basilar arteries was studied immunohistochemically using monoclonal antibodies against Ki-67. It was found that intimal thickenings (cushions) appeared immediately after birth, initially only in a few places of CAC vessel branching; by 8-10 years they were detected in all the bifurcations of the circle. With aging, the thickening of intimal cushions with a thinning of the underlying tunica media was found. Ki-67 protein expression was noted in both the intimal cushions and underlying tunica media, indicating the activity of atherosclerosis process.

Notch signaling in vascular smooth muscle cells is required to pattern the cerebral vasculature.

Stroke is the third leading cause of death and a significant contributor of morbidity in the United States. In humans, suboptimal cerebral collateral circulation within the circle of Willis (CW) predisposes to ischemia and stroke risk in the setting of occlusive carotid artery disease. Unique genes or developmental pathways responsible for proper CW formation are unknown. Herein we characterize a mouse model lacking Notch signaling in vascular smooth muscle cells (vSMCs), in which the animals are intolerant to reduced cerebral blood flow. Remarkably, unilateral carotid artery ligation results in profound neurological sequelae and death. After carotid ligation, perfusion of the ipsilateral cerebral hemisphere was markedly diminished, suggesting an anastomotic deficiency within the CW. High-resolution microcomputed tomographic (micro-CT) imaging revealed profound defects in cerebrovascular patterning, including interruption of the CW and anatomic deformity of the cerebral arteries. These data identify a vSMC-autonomous function for Notch signaling in patterning and collateral formation within the cerebral arterial circulation. The data further implicate genetic or functional deficiencies in Notch signaling in the pathogenesis of anatomic derangements underlying cerebrovascular accidents.

L-Citrulline recycle for synthesis of NO in cerebral perivascular nerves and endothelial cells.

Recycle of L-citrulline to form L-arginine in cerebral perivascular nerves has been well described, providing direct evidence that nitric oxide (NO) is synthesized and released from these nerves to act as the transmitter for vasodilation. NO is also synthesized and released from cerebral endothelial cells, involving L-citrulline conversion to L-arginine. Evidence for the presence of enzymes involved in the conversion, however, has not been shown. The presence of nitric oxide synthase (NOS), argininosuccinate synthetase (ASS), and argininosuccinate lyase (ASL), and their coexistence with NADPH-diaphorase (NADPHd), a marker for NOS, in endothelial cells of middle cerebral arteries and the circle of Willis of the pig, therefore, were examined using combined immunohistochemical and histochemical techniques. NOS-, ASS-, and ASL-immunoreactivities were found in almost all endothelial cells of all cerebral arteries examined. All ASS-, ASL-, and NOS-immunoreactive (I) endothelial cells also stained positively for NADPHd, suggesting that ASS, ASL, and NOS were colocalized in endothelial cells of middle cerebral arteries and the circle of Willis. These results provide morphological evidence that cerebral vascular endothelial cells like cerebral perivascular nerves contain enzymes necessary for recycling L-citrulline to L-arginine to synthesize NO via an argininosuccinate (AS) pathway.

Distribution of NADPH-diaphorase in the cerebral blood vessels of rats: a histochemical study.

NADPH-diaphorase (neuronal nitric oxide synthase) activity in the cerebral blood vessels was investigated by light and electron microscopic histochemistry to elucidate the sites of nitric oxide production. Networks of adventitial nerves containing NADPH-diaphorase were distributed in all parts of the circle of Willis. However, NADPH-diaphorase activity in adventitial nerves was much sparser in the region of the posterior cerebral artery, and absent in the pial arteries smaller than 100 microns in diameter. Endothelial cells were intensely stained in arteries and arterioles. These results support the hypothesis that vascular tone is regulated by nitric oxide, which is derived from endothelial cells and adventitial nerves.

Autoradiographic localization of the GABAA receptor agonist [3H]muscimol in rat cerebral vessels.

By the use of combined in vitro radioreceptor binding and autoradiographic techniques with [3H]muscimol as a ligand, we analyzed the distribution of GABAA receptor sites in the arteries of the circle of Willis as well as in the arteries and arterioles of the pial-arachnoid membrane in the rat. [3H]Muscimol was bound by sections of rat cerebral vessels in a manner consistent with the existence of GABAA receptors, with Kd and Bmax values of 46 nM and 0.60 pmol/mg tissue respectively. [3H]Muscimol was bound by the medial layer of cerebral arteries, while no specific binding was observed in the intima, the adventitia and the adventitial-medial border. These findings suggest that the vasodilatory action of GABA on in vitro preparations of cerebral vessels is mediated by muscular receptor sites. The posterior cerebral arteries are richer in [3H]muscimol binding sites than the anterior ones. Pial-arachnoid arterioles, which are of critical importance in controlling local cerebral blood flow, did not exhibit any significant binding of [3H]muscimol. These results may explain the difficulty in manipulating pharmacologically the cerebral tissue perfusion in intact animals using GABAergic agonists.