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Novel Therapeutic Approaches For Ischemic Heart And Brain Injury: Modulation Of Toll-Like Receptor-Mediated Signaling Pathways And Pi3k/Akt Signaling, Chen Lu May 2014

Novel Therapeutic Approaches For Ischemic Heart And Brain Injury: Modulation Of Toll-Like Receptor-Mediated Signaling Pathways And Pi3k/Akt Signaling, Chen Lu

Electronic Theses and Dissertations

Innate immune and inflammatory responses contribute to myocardial and cerebral ischemia/reperfusion (I/R) injury. Toll-like receptors (TLRs) play a critical role in the induction of innate immune and inflammatory responses via activation of nuclear factor kappa B (NF-κB). We have shown that activation of NF-κB contributes to myocardial and cerebral I/R injury. Indeed, inhibition of TLR4-mediated NF-κB activation significantly decreased myocardial and cerebral I/R injury via activation of PI3K/Akt signaling. PI3K/Akt signaling is an important pathway in regulating cellular survival and inflammatory responses. Therefore, an important question is how to differentially modulate PI3K/Akt signaling and TLR/NF-κB-mediated signaling pathway during I/R injury? …