Spontaneous intracerebral hemorrhage (ICH) is associated with high morbidity and mortality. Despite its clinical importance, however, there is little known about the pathogenesis of ICH and the edema that forms around it. Consequently there is no specific therapy. We intend to study the mechanisms of brain edema formation which follows acute ICH in order to develop rational treatment strategies for patients with that condition. Our proposal is based upon a highly reproducible model of ICH in the rat which we have developed. The project includes experiments designed to determine why a blood clot in brain parenchyma causes surrounding edema, increasing mass effect, and progressive neurological deterioration. We will consider two alternate, but not mutually exclusive, hypotheses. One tests the idea that brain edema following ICH results from mass effect which causes regional ischemia, disruption of the blood-brain barrier and ischemic edema. As a consequence edema control would be based primarily on elimination of mass effect caused by the clot. The experiments designed to address this hypothesis involve measurements of cerebral blood flow, brain edema, and blood-brain barrier permeability at various times after the introduction of a blood clot or an inert mass of equal volume into the caudate nucleus. The second hypothesis is based upon the idea that ICH causes an interaction between components of the clot and brain parenchyma resulting in blood-brain barrier disruption and edema formation. In this case, edema control would be more properly based on manipulation of edemagenic factors by local or systemic pharmacologic agents. Experiments will compare the effect on brain edema and blood-brain barrier permeability of the injection of specific biochemical substances that could be released from the clot and the therapeutic efficacy of treating animals with pharmacologic agents that inhibit the actions of those substances.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS017760-18
Application #
2609569
Study Section
Neurology A Study Section (NEUA)
Program Officer
Jacobs, Tom P
Project Start
1981-03-01
Project End
1999-11-30
Budget Start
1997-12-01
Budget End
1998-11-30
Support Year
18
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Surgery
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Karabiyikoglu, Murat; Hua, Ya; Keep, Richard F et al. (2013) Geldanamycin treatment during cerebral ischemia/reperfusion attenuates p44/42 mitogen-activated protein kinase activation and tissue damage. Acta Neurochir Suppl 118:39-43
Jin, Hang; Wu, Gang; Hu, Shukun et al. (2013) T2 and T2* magnetic resonance imaging sequences predict brain injury after intracerebral hemorrhage in rats. Acta Neurochir Suppl 118:151-5
Okubo, Shuichi; Xi, Guohua; Keep, Richard F et al. (2013) Cerebral hemorrhage, brain edema, and heme oxygenase-1 expression after experimental traumatic brain injury. Acta Neurochir Suppl 118:83-7
Guo, Fuyou; Hua, Ya; Wang, Jinhu et al. (2012) Inhibition of carbonic anhydrase reduces brain injury after intracerebral hemorrhage. Transl Stroke Res 3:130-7
Wang, Lin; Xi, Guohua; Keep, Richard F et al. (2012) Iron enhances the neurotoxicity of amyloid ?. Transl Stroke Res 3:107-13
Hu, Hua; Wang, Lin; Okauchi, Masanobu et al. (2011) Deferoxamine affects heat shock protein expression in heart after intracerebral hemorrhage in aged rats. Acta Neurochir Suppl 111:197-200
Ye, Zi; Xie, Qing; Xi, Guohua et al. (2011) Effects of gender on heart injury after intracerebral hemorrhage in rats. Acta Neurochir Suppl 111:119-22
Xie, Qing; Guan, Jian; Wu, Gang et al. (2011) Tamoxifen treatment for intracerebral hemorrhage. Acta Neurochir Suppl 111:271-5

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