Neuroprotection of Erythropoietin Signaling in TBI
Neuroprotection of Erythropoietin Signaling in TBI
批准号:
7018085
负责人:
CLAUDIA S ROBERTSON
金额:
$17.41万
依托单位国家:
美国
项目类别:
财政年份:
2005
资助国家:
美国
项目状态:
已结题
起止时间:
2005-12-01 至 2010-11-30
中文摘要
项目# 4。促红细胞生成素信号在脑外伤中的神经保护作用
英文摘要
PROJECT #4. Neuroprotection of Erythropoietin Signaling in TBI
Cerebral hypoperfusion plays a role in the injury that develops in contused brain. If the reduction in CBF
is severe enough, cerebral ischemic injury develops. If the reduction in CBF is not severe enough to cause
oxygen depletion, then the baseline low flow causes the brain tissue to be more vulnerable to secondary
ischemic insults. Both circumstances have a well established adverse effect on neurological outcome.
In the cortical impact injury model, cerebral hypoperfusion in contused brain is associated with a relative
deficiency of nitric oxide (NO) produced by the endothelial isoform of nitric oxide synthase (eNOS). And
administration of L-arginine (the substrate for the eNOS) or administration of tetrahydrobiopterin (an
essential cofactor of eNOS) results in an increase in the NO concentrations in the brain and restores CBF in
the contused brain back to pre-injury values. The improvement in perfusion of the contused brain with Larginine
is associated with a reduction in contusion volume.
Erythropoietin (Epo) is expressed in the brain after injury, and has several activities that might be
neuroprotective. Numerous studies suggest that Epo administration upregulates NOS or increases NO
production or dilates vessels in a manner that suggests NO production by endothelium. In physiological
circumstances where endogenous Epo production is increased, such as in athletes training at high altitudes,
production of NO is also increased. Finally in some pathological conditions, Epo administration has been
found to dilate cerebral vessels. In a subarachnoid hemorrhage model, Epo reversed the vasoconstriction
that occurred in intracranial vessels. A single dose of Epo has been shown to preserve autoregulation of
cerebral blood flow following subarachnoid hemorrhage.
The purpose of this study is to investigate these potentially neuroprotective mechanisms of Epo on the
vascular dysfunction that occurs after trauma. The specific aims include the following: To study the expression of Epo and Epo receptor (EpoR) by the injured brain. To study the acute effects of augmented Epo signaling on cerebral hemodynamics. To study the chronic effects of augmented Epo signaling on the brain's response to injury.
To study the synergistic effects of Epo and EpoR peptide administration on the brain's response to injury.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
31st Annual National Neurotrauma Society(NNS)Symposium
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批准号:8596881
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项目类别:
-
资助金额:$2.5万
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财政年份:2013
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负责人:CLAUDIA S ROBERTSON
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依托单位:
AN ERYTHROPOIETIN-MIMETIC PEPTIDE (pHBSP) FOR TREATMENT OF TBI
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批准号:8703819
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项目类别:
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资助金额:$71.6万
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财政年份:2013
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负责人:CLAUDIA S ROBERTSON
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依托单位:
AN ERYTHROPOIETIN-MIMETIC PEPTIDE (pHBSP) FOR TREATMENT OF TBI
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批准号:8437303
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项目类别:
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资助金额:$77.0万
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财政年份:2013
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Effect of Eythropoietin on Vascular Dysfunction in Human TBI
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批准号:7018083
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项目类别:
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资助金额:$26.16万
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财政年份:2006
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Role of NOS3 in the Cerebrovascular Response to TBI
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批准号:7237924
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项目类别:
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资助金额:$29.6万
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财政年份:2004
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Role of NOS3 in the Cerebrovascular Response to TBI
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批准号:6948266
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项目类别:
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资助金额:$31.22万
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财政年份:2004
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Role of NOS3 in the Cerebrovascular Response to TBI
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批准号:7061320
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项目类别:
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资助金额:$30.49万
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财政年份:2004
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Role of NOS3 in the Cerebrovascular Response to TBI
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批准号:6873344
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项目类别:
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资助金额:$31.22万
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财政年份:2004
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Regulation of Cerebral Blood Flow After Traumatic Brain Injury
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批准号:6613365
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项目类别:
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资助金额:$26.64万
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财政年份:2002
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Arginine treatment of a reduced cerebral blood flow after traumatic brain injury
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批准号:6613367
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项目类别:
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资助金额:$26.64万
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财政年份:2002
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Regulation of Cerebral Blood Flow After Traumatic Brain Injury
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批准号:6470635
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项目类别:
-
资助金额:$12.12万
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财政年份:2001
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Regulation of Cerebral Blood Flow After Traumatic Brain Injury
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批准号:6488272
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项目类别:
-
资助金额:$26.64万
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财政年份:2001
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Arginine treatment of a reduced cerebral blood flow after traumatic brain injury
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批准号:6488274
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项目类别:
-
资助金额:$26.64万
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财政年份:2001
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Arginine treatment of a reduced cerebral blood flow after traumatic brain injury
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批准号:6470637
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项目类别:
-
资助金额:$12.12万
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财政年份:2001
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Arginine treatment of a reduced cerebral blood flow after traumatic brain injury
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批准号:6347679
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项目类别:
-
资助金额:$12.12万
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财政年份:2000
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Regulation of Cerebral Blood Flow After Traumatic Brain Injury
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批准号:6346312
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项目类别:
-
资助金额:$20.36万
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财政年份:2000
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Arginine treatment of a reduced cerebral blood flow after traumatic brain injury
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批准号:6346314
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项目类别:
-
资助金额:$20.36万
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财政年份:2000
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Regulation of Cerebral Blood Flow After Traumatic Brain Injury
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批准号:6347677
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项目类别:
-
资助金额:$12.12万
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财政年份:2000
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负责人:CLAUDIA S ROBERTSON
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依托单位:
Vascular Mechanisms of Secondary Injury After TBI
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批准号:7204160
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项目类别:
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资助金额:$116.73万
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财政年份:1999
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负责人:CLAUDIA S ROBERTSON
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依托单位:
VASC MECHS OF SECONDARY INSULTS IN SEVERE BRAIN INJURY
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批准号:6484283
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项目类别:
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资助金额:$5.1万
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财政年份:1999
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负责人:CLAUDIA S ROBERTSON
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依托单位:
海外基金