000000407 001__ 407 000000407 005__ 20260306121244.0 000000407 0247_ $$2DOI$$a10.6083/M48G8HNW 000000407 037__ $$aETD 000000407 245__ $$aPreconditioning reprograms TLR signaling following cerebral ischemia the emergence of a neuroprotective program 000000407 260__ $$bOregon Health and Science University 000000407 269__ $$a2008 000000407 336__ $$aDissertation 000000407 502__ $$bPh.D. 000000407 520__ $$aLPS preconditioning, achieved by administering a small dose of lipopolysaccharide before stroke, produces strong neuroprotection, likely through Toll like receptor 4 (TLR4) signaling and TNFα induction. Because stroke triggers endogenous TLR activation, with some TLRs worsening injury and others promoting protection, this study tested whether additional TLR ligands can shift post ischemic signaling toward neuroprotection. Systemic preconditioning with CpG oligodeoxynucleotides, a TLR9 ligand, significantly reduced ischemic damage in vivo and protected neurons in vitro. CpG treatment elevated serum TNFα and required TNFα for its effects. These findings show that multiple TLR ligands can induce TNFα dependent neuroprotection against stroke. 000000407 540__ $$fCC BY 000000407 542__ $$fIn copyright - single owner 000000407 650__ $$aToll-Like Receptors$$036751 000000407 650__ $$aStroke$$032460 000000407 650__ $$aNeuroprotective Agents$$031018 000000407 650__ $$aDrug Therapy$$018086 000000407 650__ $$aNeuroprotection$$011086 000000407 650__ $$aLipopolysaccharides$$021552 000000407 691__ $$aSchool of Medicine$$041369 000000407 692__ $$aDepartment of Molecular Microbiology and Immunology$$041429 000000407 7001_ $$aMarsh, Brenda$$uOregon Health and Science University$$041354 000000407 7201_ $$aStenzel-Poore, Mary$$uOregon Health and Science University$$041354$$7Personal$$eMentor 000000407 8564_ $$9f99741de-2dc3-47bd-b6c6-8b26d4185471$$s2711237$$uhttps://digitalcollections.ohsu.edu/record/407/files/408_etd.pdf$$ePublic$$24a3708a228b606e73eb7e2e5388fbc50$$31 000000407 905__ $$a/rest/prod/2f/75/r8/06/2f75r806g 000000407 909CO $$ooai:digitalcollections.ohsu.edu:407$$pstudent-work 000000407 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument 000000407 980__ $$aTheses and Dissertations