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Gene Expression Profiling in Human Acute Ischemic Stroke

Barr, Taura Lynn (2009) Gene Expression Profiling in Human Acute Ischemic Stroke. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Background: Gene expression profiling of human acute ischemic stroke (AIS) has the potential to identify a diagnostic panel for differential diagnosis of AIS early in the treatment phase. Purpose: The objective of this dissertation was to identify peripheral blood biomarkers that could be further explored for use in differential diagnosis of AIS and the design of stroke therapeutics.Methods: A prospective gene expression profiling study of 39 patients and 25 healthy controls was conducted. Peripheral blood samples were collected in Paxgene Blood RNA tubes from patients who were ≥18 years of age with MRI diagnosed AIS after differential diagnosis and controls who were Non-stroke neurologically healthy. In stroke patients, blood was redrawn 24 hours following onset of symptoms to determine changes in gene expression profiles over time. RNA was hybridized to Illumina humanRef-8v2 bead chips. Validation was performed using Taqman Gene expression polymerase chain reaction on significant targets. Results: A nine gene profile has been identified for AIS. Five of these nine genes were identified in the previously published whole blood gene expression profiling study of stroke and therefore play a likely role in the response to AIS in humans. One of these nine genes (s100A12) was significantly associated with increasing age and therefore may be non-specific for stroke. Three genes were identified as the whole blood expression profile change over time (LY96, IL8, and SDPR). Pathway analysis revealed a robust innate immune response, with toll like receptor (TLR) signaling as a highly significant pathway present in the peripheral whole blood of AIS patients.Conclusion: The findings of this study support the claim that gene expression profiling of peripheral whole blood can be used to identify diagnostic markers of AIS. A plausible case for innate immunity through the activation of TLR4 as a mediator of response to AIS has been made from the results of this study. This study and those conducted by Moore et al (2005) and Tang et al (2006) provide the foundation of data that support the use of peripheral whole blood for future blood profiling studies of neurological disease; which significantly opens the door of opportunity.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Barr, Taura
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairConley, Yvetteyconley@pitt.eduYCONLEY
Committee MemberSingleton,
Committee MemberDing,
Committee MemberHenker, Richardrhe001@pitt.eduRHE001
Committee MemberAlexander, Sheilasalexand@pitt.eduSALEXAND
Committee MemberWarach,
Date: 25 April 2009
Date Type: Completion
Defense Date: 20 April 2009
Approval Date: 25 April 2009
Submission Date: 24 April 2009
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: School of Nursing > Nursing
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: biomarkers; gene expression; ischemic stroke
Other ID:, etd-04242009-124645
Date Deposited: 10 Nov 2011 19:42
Last Modified: 15 Nov 2016 13:42


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