Pial Vessel Permeability to Tracers Using Cranial Windows

2003 ◽  
pp. 121-132
Author(s):  
William G. Mayhan
Keyword(s):  
Vessel Permeability ◽  
Pial Vessel

ROLE OF NITRIC OXIDE IN RAT PIAL VESSEL DILATATION RESPONSE TO ISOFLURANE

1993 ◽  
Vol 5 (4) ◽  
pp. 290 ◽  
Author(s):  
H. M. Koenig ◽  
D. A. Pelligrino ◽  
O. Wang ◽  
R. F. Albrecht
Keyword(s):  
Nitric Oxide ◽  
Vessel Dilatation ◽  
Pial Vessel

Mice overexpressing placenta growth factor exhibit increased vascularization and vessel permeability

2002 ◽  
Vol 115 (12) ◽  
pp. 2559-2567 ◽  
Author(s):  
Teresa Odorisio ◽  
Cataldo Schietroma ◽  
M. Letizia Zaccaria ◽  
Francesca Cianfarani ◽  
Cecilia Tiveron ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Adult Life ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Placenta Growth Factor ◽  
Vessel Permeability ◽  
Exact Function ◽  
Endothelial Growth Factor

Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family, comprising at least five cytokines specifically involved in the regulation of vascular and/or lymphatic endothelium differentiation. Several lines of evidence indicate a role for PlGF in monocyte chemotaxis and in potentiating the activity of VEGF, but the exact function of this cytokine is not fully understood. To define the biological role of PlGF in vivo, we have produced a transgenic mouse model overexpressing this factor in the skin by using a keratin 14 promoter cassette. Our data indicate that PlGF has strong angiogenic properties in both fetal and adult life. PlGF overexpression results in a substantial increase in the number,branching and size of dermal blood vessels as well as in enhanced vascular permeability. Indeed, intradermally injected recombinant PlGF was able to induce vessel permeability in wild-type mice. The analysis of vascular endothelial growth factor receptor 1/flt-1 and vascular endothelial growth factor receptor 2/flk-1 indicates that the two receptors are induced in the skin endothelium of transgenic mice suggesting that both are involved in mediating the effect of overexpressed PlGF.

scholarly journals Modulating Sphingosine-1-Phosphate receptors to improve chemotherapy delivery to Ewing sarcoma

2019 ◽  
Author(s):  
Enrica Marmonti ◽  
Hannah Savage ◽  
Aiqian Zhang ◽  
Claudia Alvarez ◽  
Miriam Morrell ◽  
...  
Keyword(s):  
G Protein ◽  
Ewing Sarcoma ◽  
Tyrosine Kinases ◽  
Tumor Vasculature ◽  
Cell Junction ◽  
Tumor Vessels ◽  
S1p Receptors ◽  
Vessel Permeability ◽  
Sphingosine 1 Phosphate ◽  
G Protein Coupled

ABSTRACTTumor vasculature is innately dysfunctional. Poorly functional tumor vessels inefficiently deliver chemotherapy to tumor cells; vessel hyper-permeability promotes chemotherapy delivery primarily to a tumor’s periphery. Here we identify a method for enhancing chemotherapy delivery and efficacy in Ewing sarcoma (ES) in mice by modulating tumor vessel permeability. Vessel permeability is partially controlled by the G protein-coupled Sphinosine-1-phosphate receptors 1 and 2 (S1PR1 and S1PR2) on endothelial cells. S1PR1 promotes endothelial cell junction integrity while S1PR2 destabilizes it. We hypothesize that an imbalance of S1PR1:S1PR2 is partially responsible for the dysfunctional vascular phenotype characteristic of ES and that by altering the balance in favor of S1PR1, ES vessel hyper-permeability can be reversed. In this study, we demonstrate that pharmacologic activation of S1PR1 by SEW2871 or inhibition of S1PR2 by JTE-013 caused more organized, mature, and functional tumor vessels. Importantly, S1PR1 activation or S1PR2 inhibition improved chemotherapy delivery to the tumor and anti-tumor efficacy. Our data suggests that pharmacologic targeting of S1PR1 and S1PR2 may be a useful adjuvant to standard chemotherapy for ES patients.NOVELTY AND IMPACTThis study demonstrates that Sphingosine-1-Phosphate (S1P) receptors are potential novel targets for tumor vasculature remodeling and adjuvant therapy for the treatment of Ewing Sarcoma. Unlike receptor tyrosine kinases that have already been extensively evaluated for use as vascular normalizing agents in oncology, S1P receptors are G protein-coupled receptors, which have not been well studied in tumor endothelium. Pharmacologic activators and inhibitors of S1P receptors are currently in clinical trials for treatment of auto-immune and cardiovascular diseases, indicating potential for clinical translation of this work.

scholarly journals Increased Microvascularization and Vessel Permeability Associate With Active Inflammation in Human Atheromata

2014 ◽  
Vol 7 (6) ◽  
pp. 920-929 ◽  
Author(s):  
Viviany R. Taqueti ◽  
Marcelo F. Di Carli ◽  
Michael Jerosch-Herold ◽  
Galina K. Sukhova ◽  
Venkatesh L. Murthy ◽  
...  
Keyword(s):  
Vessel Permeability ◽  
Active Inflammation

Activated oxygen and arachidonate effects on newborn cerebral arterioles

1990 ◽  
Vol 259 (4) ◽  
pp. H1230-H1238 ◽  
Author(s):  
C. W. Leffler ◽  
D. W. Busija ◽  
W. M. Armstead ◽  
D. R. Shanklin ◽  
R. Mirro ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Ultrastructural Changes ◽  
Brain Surface ◽  
Activated Oxygen ◽  
Strong Stimulation ◽  
Pial Arterioles ◽  
Cerebral Arterioles ◽  
Direct Generation ◽  
Pial Vessel

We have observed that pial arteriolar dilation in response to hypercapnia and hypotension is abolished after cerebral ischemia in newborn pigs. We determined whether direct generation of activated oxygen on the brain surface (OX: xanthine oxidase, hypoxanthine, FeCl3, and FeSO4) or topical arachidonate altered pial arteriolar responsiveness in a manner similarly to cerebral ischemia. OX, which generated more brain surface superoxide than reperfusion after ischemia, dilated pial arterioles. This dilation was reversed within 10 min of the end of exposure. OX produced ultrastructural changes in pial vessel endothelium and appeared to cause intravascular aggregation of granulocytes. After OX, prostanoid-dependent pial arteriolar dilations in response to hypercapnia and hypotension were attenuated, whereas constrictor responses to norepinephrine and acetylcholine and dilator responses to prostaglandin E2 and isoproterenol were not affected. After OX, hypercapnia increased cortical periarachnoid cerebrospinal fluid prostanoids modestly, whereas acetylcholine produced the normal strong stimulation of prostanoid synthesis. Arachidonate (10(-4) M and 7 x 10(-4) M) also caused reversible pial arteriolar dilation but did not alter subsequent pial arteriolar responses. Therefore, although arachidonate did not mimic the effects of ischemia-reperfusion on pial arteriolar reactivity, OX produced alterations that are qualitatively similar, although quantitatively less, than those produced by ischemia.

Effect of postischemic hypoperfusion on vasodilatory mechanisms in cats

1994 ◽  
Vol 267 (5) ◽  
pp. H2012-H2018 ◽  
Author(s):  
N. Clavier ◽  
J. R. Kirsch ◽  
P. D. Hurn ◽  
R. J. Traystman
Keyword(s):  
Vascular Reactivity ◽  
Signal Transduction Pathway ◽  
Global Cerebral Ischemia ◽  
Transduction Pathway ◽  
Muscarinic Agonists ◽  
No Donor ◽  
A 23187 ◽  
Muscarinic Stimulation ◽  
Arterial Dilation ◽  
Pial Vessel

We addressed the mechanism for reduced pial vascular reactivity to muscarinic stimulation by evaluating pial vessel responses to receptor-dependent [10(-5) M acetylcholine (ACh)] and independent (10(-5) M A-23187) agonists and the endothelium-independent nitric oxide (NO) donor [10(-5) M nitroprusside (NP)]. Cerebral blood flow (CBF, microspheres) and pial arteriolar diameters (intravital microscopy) were measured in halothane-anesthetized cats. Cats (n = 13) were treated with 12 min of near-complete global cerebral ischemia, whereas control animals (n = 9) were identically instrumented but were not submitted to ischemia. Postischemic hypoperfusion was evident in most animals at 60 min of reperfusion, accompanied by attenuated pial arterial dilation to topical ACh (baseline dilation 23 +/- 4% vs. postischemia 11 +/- 3%) and A-23187 (16 +/- 4 vs. 0 +/- 3% dilation). Dilation to NP was unaffected. CBF response to intravenous administration of the muscarinic receptor agonist oxotremorine was also decreased throughout the forebrain (162 +/- 12 vs. 116 +/- 6% increase in flow) in these cats. These data suggest that endothelium-dependent vasodilation with topical muscarinic agonists is impaired during hypoperfusion, but vascular smooth muscle responsivity to NO remains intact. We conclude that the defect in the signal transduction pathway is not limited to the receptor and may involve an abnormality with NO synthesis or its destruction within endothelium.

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