The long term goal of this research is to understand how the growth of blood vessels in the brain is controlled. Endothelium is a vital cellular component of the nervous system, is the conduit for circulation and exchange of metabolites, is the major interface of the blood-brain barrier, and has important chemical and regulatory functions. The cellular and molecular mechanisms which regulate the growth of brain endothelium during normal angiogenesis are uncertain. These mechanisms relate to congenital arteriovenous malformations, which arise from errors during brain angiogenesis, and to brain hemangioblastomas, in which proliferation of endothelial-like cells is uncontrolled. In addition, insufficient capillary growth in the retina of premature infants may initiate retrolental fibroplasia and blindness. Finally, brain tumors depend upon angiogenesis from brain endothelium for their growth and survival and might be controlled by inhibiting these mechanisms. The model selected for brain angiogenesis is the transparent albino Xenopus laevis tadpole. The structure of individual capillaries on the surface of the optic tectum can be resolved by light microscopy in vivo. The first specific aim is to chart the growth of the network of blood vessels in individual tadpoles from stage 43 with only a few capillaries through the major 4-6 week period of angiogenesis as the optic tectum grows about 10-fold in surface area. Second, quantitative determinations will be made for density of capillary sprouts, intratectal vascular branches, and capillary lengths per surface area. Third, angiogenic growth factors and inhibitors will be injected into the blood, ventricular fluid, and pial spaces with micropipettes to alter the growth of tectal blood vessels. Fourth, antisera and monoclonal antibodies will be produced against Xenopus endothelium as developmental markers. A fifth aim is to culture capillary endothelium, macrophages, and pericytes from the same albino strain of Xenopus and to test angiogenic responses in vitro and interactions of marked cells with brain angiogenesis in vivo.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL041075-02
Application #
3358541
Study Section
Pathology A Study Section (PTHA)
Project Start
1988-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Wei, L; Erinjeri, J P; Rovainen, C M et al. (2001) Collateral growth and angiogenesis around cortical stroke. Stroke 32:2179-84
Moskalenko YuE; Rovainen, C; Woolsey, T A et al. (1996) Comparison of measurements of local brain blood flow by hydrogen clearance with the inhalation of hydrogen and its electrochemical generation in brain tissue. Neurosci Behav Physiol 26:245-50
Moskalenko, Y E; Dowling, J L; Liu, D et al. (1996) LCBF changes in rat somatosensory cortex during whisker stimulation monitored by dynamic H2 clearance. Int J Psychophysiol 21:45-59
Tang, Y Y; Rovainen, C M (1996) Cardiac output in Xenopus laevis tadpoles during development and in response to an adenosine agonist. Am J Physiol 270:R997-1004
Rovainen, C M (1996) Feeding and breathing in lampreys. Brain Behav Evol 48:297-305
Wei, L; Rovainen, C M; Woolsey, T A (1995) Ministrokes in rat barrel cortex. Stroke 26:1459-62
Moskalenko, Iu E; Rovainen, C M; Woolsey, T A et al. (1994) [A comparison of the measurements of local cerebral blood flow by hydrogen clearance with hydrogen inhalation and by its electrochemical generation in brain tissue] Fiziol Zh Im I M Sechenova 80:119-26
Jen, S C; Rovainen, C M (1994) An adenosine agonist increases blood flow and density of capillary branches in the optic tectum of Xenopus laevis tadpoles. Microcirculation 1:59-66
Moskalenko, Iu E; Rovainen, C M; Woolsey, T A et al. (1994) [Combinations of methods for the monitoring of the cerebral microcirculation] Fiziol Zh Im I M Sechenova 80:144-53
Rovainen, C M; Woolsey, T A; Blocher, N C et al. (1993) 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. J Cereb Blood Flow Metab 13:359-71

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