Loading...
Early thrombopoietin intervention in stroke: Requirement for thrombopoietin receptor for brain and behavioral protection.
Journal Title
Keywords
Readers/Advisors
Barone, Frank
Journal Title
Term and Year
Fall 2013
Publication Date
2013-12-18
Book Title
Publication Volume
Publication Issue
Publication Begin
Publication End
Number of pages
Files
Loading...
Doctoral Dissertation
Adobe PDF, 35.61 MB
Research Projects
Organizational Units
Journal Issue
Abstract
Cerebral ischemia results in brain injury. The brain inflammatory response to ischemia contributes significantly to stroke-induced ischemic injury. Thrombopoietin (TPO), a hematopoietic growth factor that regulates platelet production, has recently been reported to protect the rat from ischemic stroke brain injury and associated behavioral deficits. My research has focused on early post-stroke TPO intervention using a mouse stroke model. Here I present data that addresses TPOs brain- and behavioral-protective effects in mouse ischemic stroke. I found that TPO treatment in WT mice produces significant protection from ischemic hemisphere swelling (57.4 ± 6.5%), hemisphere infarction (43.2 ± 5.2%), neurological deficits (36.9 ± 12.6%) and provides significant preservation of post-stroke cognitive functioning. No TPO protection was observed in TPOR KO mice. IHC data indicates that TPO significantly reduced peri-infarct up-regulation of TNF(40.4 ± 10.2%) and MMP-9 (27.1 ± 11.1%) in microvascular endothelium. Furthermore, peri-infarct vascular neutrophil infiltration into brain (25.1 ± 3.4%) and microgliosis (35.4 ± 6.5%) were inhibited by TPO. In addition to reducing brain infarction and swelling, TPO also acts to reduce microvascular inflammation and thereby to preserve the blood brain barrier. In TPOR KO mice, TPO treatment neither attenuated increased microvascular TNFor MMP-9, nor inhibited neutrophil infiltration or microgliosis. Thus, I have demonstrated that the TPOR is required for TPO brain protection from stroke-induced injury and behavioral deficits. Mechanistically, TPO treatment reduces the microvascular and parenchymal brain inflammatory response to stroke resulting in protection of the brain and blood brain barrier resulting in preservation of functioning on all levels examined.
Citation
Zhuang, J. (2013). Early thrombopoietin intervention in stroke: Requirement for thrombopoietin receptor for brain and behavioral protection. [Doctoral dissertation, SUNY Downstate Health Sciences University]. SUNY Open Access Repository. https://soar.suny.edu/handle/20.500.12648/16207
DOI
Description
Doctoral Dissertation