Blood flow within the brain is characterized by dynamic spatial and temporal control. The constantly shifting patterns of regional neuronal activity and the high energy demands of active neurons necessitate local mechanisms capable of regulating blood flow in a rapid and precise manner. Parenchymal microvessels are the final cerebrovascular elements responsible for supplying these needs; however, the local mechanisms through which these vessels are regulated are poorly understood. The overall goal of this application is to improve our understanding of how local mechanisms within the brain parenchyma regulate microvascular function under physiological and pathophysiological circumstances. During the initial period of support for this work, we have: 1) developed and tested novel approaches for examining parenchymal microvessels within their normal cellular microenvironment, 2) identified key local mechanisms involved in the regulation of cerebral microvascular tone, and 3) begun to examine how microvascular function is disturbed during metabolic challenge such as occurs after stroke.
The Specific Aims of this proposal are to: 1) characterize the roles of local neurons and glia in the regulation of parenchymal microvessels, and 2) elucidate pathophysiological mechanisms contributing to microvascular dysfunction. The proposed studies will provide insights into a fundamental form of intercellular signalling that is involved in coupling local blood flow to local neuronal activity in the brain. A clear understanding of the physiology nd pathophysiology of microvascular control will help identify novel strategies for limiting secondary ischemic injury to the brain.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
3R01HL049396-04S1
Application #
2908741
Study Section
Neurology A Study Section (NEUA)
Project Start
1994-12-01
Project End
2000-11-30
Budget Start
1998-02-20
Budget End
1998-11-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Virginia
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Chang, Chih-Zen; Winardi, Daniel; Lin, Chih-Lung et al. (2002) Attenuation of hemolysate-induced cerebrovascular endothelial cell injury and of production of endothelin-1 and big endothelin-1 by an endothelin-converting enzyme inhibitor. Surg Neurol 58:181-7; discussion 187-8
Chen, Z F; Kamiryo, T; Henson, S L et al. (2001) Anticonvulsant effects of gamma surgery in a model of chronic spontaneous limbic epilepsy in rats. J Neurosurg 94:270-80
Kamiryo, T; Lopes, M B; Kassell, N F et al. (2001) Radiosurgery-induced microvascular alterations precede necrosis of the brain neuropil. Neurosurgery 49:409-14; discussion 414-5
Kwan, A L; Lin, C L; Wu, C S et al. (2000) Delayed administration of the K+ channel activator cromakalim attenuates cerebral vasospasm after experimental subarachnoid hemorrhage. Acta Neurochir (Wien) 142:193-7
Toyoda, T; Kassell, N F; Lee, K S (2000) Induction of tolerance against ischemia/reperfusion injury in the rat brain by preconditioning with the endotoxin analog diphosphoryl lipid A. J Neurosurg 92:435-41
Nishio, S; Yunoki, M; Chen, Z F et al. (2000) Ischemic tolerance in the rat neocortex following hypothermic preconditioning. J Neurosurg 93:845-51
Nishio, S; Chen, Z F; Yunoki, M et al. (1999) Hypothermia-induced ischemic tolerance. Ann N Y Acad Sci 890:26-41
Toyoda, T; Kwan, A L; Bavbek, M et al. (1998) Enhanced endogenous antioxidant activity and inhibition of cerebral vasospasm in rabbits by pretreatment with a nontoxic endotoxin analog, monophosphoryl lipid A. J Neurosurg 88:1082-7
Bavbek, M; Polin, R; Kwan, A L et al. (1998) Monoclonal antibodies against ICAM-1 and CD18 attenuate cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. Stroke 29:1930-5;discussion 1935-6
Polin, R S; Bavbek, M; Shaffrey, M E et al. (1998) Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage. J Neurosurg 89:559-67

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