Blood Flow in Single Surface Arterioles and Venules on the Mouse Somatosensory Cortex Measured with Videomicroscopy, Fluorescent Dextrans, Nonoccluding Fluorescent Beads, and Computer-Assisted Image Analysis

Rovainen, Carl M.; Woolsey, Thomas A.; Blocher, Nissa C.; Wang, Dan-Bing; Robinson, Orlando F.

doi:10.1038/jcbfm.1993.49

Cited by 73 publications

(54 citation statements)

References 19 publications

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“…Techniques for measurement of amniotic fluid flow into the lung are not available; however, fluorescently labeled polystyrene beads were successfully used previously to measure blood flow (Rovainen et al, 1993). This technology was adapted to evaluate amniotic fluid flow into the fetal lung.…”

Section: Cftr Overexpression Effect On Muscle Contractionmentioning

confidence: 99%

Cystic fibrosis transmembrane conductance regulator (CFTR) dependent cytoskeletal tension during lung organogenesis

Cohen

Larson

2006

Developmental Dynamics

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There is growing evidence for the role of CFTR (cystic fibrosis transmembrane conductance regulator) in lung development and differentiation. The mechanism by which the chloride channel could affect lung organogenesis, however, is unknown. In utero CFTR gene transfer in the fetal lungs of mice, rats, and non-human primates was shown previously to alter lung structure and function. A study of the genes altered in the fetal rat lung following CFTR overexpression was initiated in an effort to determine the molecular mechanism for CFTR-dependent differentiation. In utero gene transfer with recombinant adenoviruses carrying either a reporter gene or CFTR resulted in the increased expression of a number of genes upon microarray analysis. The majority of the genes overexpressed in the CFTR-treated lungs were primarily associated with muscle structure and function. Histological and biochemical characterization of these proteins including myosin heavy chain, heat shock protein 27, and isoforms of myosin light chain showed that CFTR overexpression had a profound effect on smooth muscle contraction-related proteins. The CFTR-dependent regulation of smooth muscle contraction related proteins was shown to be related to chloride and extracellular ATP and was dependent upon the PI3 Kinase and Phospholipase C pathways. The changes in smooth muscle proteins were consistent with CFTR-dependent contractions of the embryonic airway smooth muscle. An assay was developed using fluorescent polystyrene beads to show that CFTR did indeed increase amniotic fluid flow into the fetal lung. Increased amniotic fluid pressure was shown previously to be associated with stretch-induced differentiation of the lung. Evaluation of neonatal respiratory function showed that CFTR-dependent muscle contractions and increased amniotic fluid pressure resulted in accelerated maturation of the neonatal rat lung. In addition, these CFTR-dependent changes were shown to be sufficient to reverse the lung phenotype of the CFTR knockout mouse. Mechanical forces influence lung development through pulmonary distension. CFTR overexpression in the fetal lung altered differentiation and development in the lung. These results are consistent with CFTR influencing lung development by regulating the muscle contractions associated with cytoskeletal tension and stretch induced differentiation. Deficiency of CFTR altering lung development would contribute significantly to the Cystic Fibrosis disease phenotype.

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Section: Cftr Overexpression Effect On Muscle Contractionmentioning

confidence: 99%

Cystic fibrosis transmembrane conductance regulator (CFTR) dependent cytoskeletal tension during lung organogenesis

Cohen

Larson

2006

Developmental Dynamics

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“…RBC velocity was determined via analysis of the velocity of 1-mdiameter fluorescent polystyrene microspheres (FluoSpheres, yellow/ green; Molecular Probes, Eugene, OR) injected i.v. in 10 l boluses (23). Beads were visualized via epifluorescence as for FITC dextran.…”

Section: Intravital Microscopymentioning

confidence: 99%

Critical Role of the α4 Integrin/VCAM-1 Pathway in Cerebral Leukocyte Trafficking in Lupus-Prone MRL/faslprMice

James

Bullard

Hickey

2003

The Journal of Immunology

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MRL/faslpr mice are affected by a systemic autoimmune disease that results in leukocyte recruitment to a wide range of vascular beds, including the cerebral microvasculature. The mechanisms responsible for the leukocyte trafficking to the brain in these animals are not known. Therefore, the aim of this study was to directly examine the cerebral microvasculature in MRL/faslpr mice and determine the molecular mechanisms responsible for this leukocyte recruitment. Intravital microscopy was used to assess leukocyte-endothelial cell interactions (rolling, adhesion) in the pial microcirculation of MRL+/+ (control) and MRL/faslpr mice at 8, 12, and 16 wk of age. Leukocyte rolling and adhesion were rarely observed in MRL+/+ mice of any age. MRL/faslpr mice displayed similar results at 8 and 12 wk. However, at 16 wk, significant increases in leukocyte rolling and adhesion were observed in these mice. Histological analysis revealed that the interacting cells were exclusively mononuclear. Leukocyte rolling was reduced, but not eliminated in P-selectin−/−-MRL/faslpr mice. However, leukocyte adhesion was not reduced in these mice, indicating that P-selectin-dependent rolling was not required for leukocyte recruitment to the cerebral vasculature in this model of systemic inflammation. E-selectin blockade also had no effect on leukocyte rolling. In contrast, blockade of either the α4 integrin or VCAM-1 eliminated P-selectin-independent leukocyte rolling. α4 Integrin blockade also significantly inhibited leukocyte adhesion. These studies demonstrate that the systemic inflammatory response that affects MRL/faslpr mice results in leukocyte rolling and adhesion in the cerebral microcirculation, and that the α4 integrin/VCAM-1 pathway plays a central role in mediating these interactions.

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“…In contrast to the substantial interconnections within the surface and subsurface networks, the penetrating arterioles that bridge these networks appear to be largely devoid of anastomoses (4,9). This architecture casts the penetrating arterioles as a singular element for the regulation of blood flow to columnar-sized regions of cortex (10)(11)(12). Yet this very same feature is likely to cause pronounced ischemia if the penetrating arterioles are occluded.…”

mentioning

confidence: 99%

Penetrating arterioles are a bottleneck in the perfusion of neocortex

Nishimura

Schaffer²,

Friedman³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

327

309

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Penetrating arterioles bridge the mesh of communicating arterioles on the surface of cortex with the subsurface microvascular bed that feeds the underlying neural tissue. We tested the conjecture that penetrating arterioles, which are positioned to regulate the delivery of blood, are loci of severe ischemia in the event of occlusion. Focal photothrombosis was used to occlude single penetrating arterioles in rat parietal cortex, and the resultant changes in flow of red blood cells were measured with two-photon laser-scanning microscopy in individual subsurface microvessels that surround the occlusion. We observed that the average flow of red blood cells nearly stalls adjacent to the occlusion and remains within 30% of its baseline value in vessels as far as 10 branch points downstream from the occlusion. Preservation of average flow emerges 350 m away; this length scale is consistent with the spatial distribution of penetrating arterioles. We conclude that penetrating arterioles are a bottleneck in the supply of blood to neocortex, at least to superficial layers.blood flow ͉ hemodynamics ͉ ischemia ͉ stroke ͉ two photon

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Blood Flow in Single Surface Arterioles and Venules on the Mouse Somatosensory Cortex Measured with Videomicroscopy, Fluorescent Dextrans, Nonoccluding Fluorescent Beads, and Computer-Assisted Image Analysis

Cited by 73 publications

References 19 publications

Cystic fibrosis transmembrane conductance regulator (CFTR) dependent cytoskeletal tension during lung organogenesis

Cystic fibrosis transmembrane conductance regulator (CFTR) dependent cytoskeletal tension during lung organogenesis

Critical Role of the α4 Integrin/VCAM-1 Pathway in Cerebral Leukocyte Trafficking in Lupus-Prone MRL/faslprMice

Penetrating arterioles are a bottleneck in the perfusion of neocortex

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