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Biomedical subjects

L Schilling

Publications and source records attributed to L Schilling.

77 records · Page 5Linked to original sources
PubMedDate not supplied

Lack of effect of topically applied nicotine on pial arteriole diameter and blood-brain barrier integrity in the cat.

In the present study, the vasomotor effects of nicotine, its interaction with local chemical factors and norepinephrine, and its effects on the permeability of the blood-brain barrier (BBB) were investigated. Using perivascular microapplication, 10(-6) M nicotine was found not to exert a vasomotor effect by itself or to modify the vasodilating effect of an increase in perivascular H+, K+ and adenosine concentration. The constrictor effect of a decrease in H+, K+ or an increase in norepinephrine concentration in the perivascular space was also not altered by 10(-6) M nicotine, indicating a lack of interaction between nicotine and the compounds tested. Using cortical superfusion and intravital fluorescence microscopy nicotine (10(-7) to 10(-3) M) was also found not to affect the diameter of pial arteries during superfusion periods of 30 min each. The integrity of BBB could be demonstrated in time-matched solvent controls over 3 h using intravenously-infused FITC-labelled dextran (MW 70,000) as tracer. During cortical superfusion with 10(-7) to 10(-5) M nicotine the permeability of the BBB was not increased compared with the time-matched controls. However, during superfusion with 10(-4) and 10(-3) M nicotine, tracer extravasation could be quantified by computer-aided image analysis. The extravasation index (EI) increased by up to eight times. These data indicate that only toxic concentrations of nicotine increase BBB permeability to FITC-dextran 70,000.

Adenosine↗
PubMedDate not supplied

Glioma cell migration is associated with glioma-induced angiogenesis in vivo.

To simultaneously assess glioma cell invasion and glioma angiogenesis in vivo by non-invasive and quantitative means, DiI-labeled C6 glioma spheroids were implanted into the dorsal skinfold chamber preparation of nude mice (n = 6). Heat-inactivated spheroids served as controls to distinguish between active and passive cell spread. Using multi-fluorescent intravital videomicroscopy, glioma cell migration was analyzed on days 1-4, 6, and 10 and spheroid vascularization was analyzed on days 3, 6, and 10 after implantation. Additionally, C6 glioma spheroids were implanted into the chronic cranial window of nude mice as an orthotopic implantation site (n = 4). In the dorsal skinfold chamber, spheroids were vascularized within 10 days and revealed a tumor-specific microvasculature. In parallel, individual glioma cells detached from the spheroid edge and migrated centrifugally demonstrating an affinity to tumor and host vessels. Glioma cells demonstrated a heterogeneous pattern of their regional migratory activity (0.2-9.6 microm/h) which correlated well with regional glioma angiogenesis (r = 0.733). Using the cranial window, glioma cells spread similarly demonstrating an affinity to the perivascular space of pial/subpial vessels with preference to the arteriolar segments. Intravital fluorescence microscopy represents a versatile technique to assess the complex relationship between glioma-driven angiogenesis and glioma cell invasion.

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PubMedDate not supplied

New developments in the understanding of cerebral vasoregulation and vasospasm: the endothelin-nitric oxide network.

Endothelins, which are powerful vasoconstrictors, and nitric oxide, which is a powerful vasodilator, together form a balanced system that regulates blood flow in the brain and in other organs. Ongoing research may yield new drugs that act on this system to prevent or reverse cerebral vasospasm in subarachnoid hemorrhage and other conditions. Many compounds are involved in cerebral vasoregulation under physiologic and pathologic conditions; of these, endothelins and nitric oxide have attracted considerable attention over the last several years. Endothelins and nitric oxide differ in chemical structure and pharmacological properties: endothelins are potent vasoconstrictor peptides consisting of 21 amino acids; nitric oxide is a free radical with a half-life of only a few seconds and exerts powerful vasodilatory effects. Both are produced by a number of cell types in the brain and interact at various levels to profoundly influence cerebral vessel function.

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