| First Author | Famakin BM | Year | 2011 |
| Journal | Brain Res | Volume | 1388 |
| Pages | 148-56 | PubMed ID | 21376021 |
| Mgi Jnum | J:172528 | Mgi Id | MGI:5008217 |
| Doi | 10.1016/j.brainres.2011.02.074 | Citation | Famakin BM, et al. (2011) Disruption of downstream MyD88 or TRIF Toll-like receptor signaling does not protect against cerebral ischemia. Brain Res 1388:148-56 |
| abstractText | Toll-like receptor (TLR) signaling plays an important role in cerebral ischemia, but downstream signaling events, which can be organ-specific, are incompletely understood. We thereby investigated involvement of the MyD88-dependent (MyD88) and MyD88-independent (TRIF) TLR signaling pathways in 2 in vitro and 2 in vivo models of cerebral ischemia. For in vitro studies, we used a model of oxygen-glucose deprivation (OGD) followed by flow cytometric analysis to determine:1) viability of PC12 cells following knock-down with MyD88 siRNA compared to negative control siRNA and 2) viability, apoptosis and necrosis of cortical neurons from MyD88 null (-/-) , TRIF mutant, and wild type (WT) mice. In addition, in vivo, 1) We examined CA1 neuronal survival 7 days after global forebrain ischemia and 2) infarct volumes 24h after Middle Cerebral Artery Occlusion (MCAO) in all 3 types of mice. OGD: 1) There were no differences in either percent viability of PC12 cells transfected with MyD88 compared to negative control siRNA or 2) in percent viability, apoptosis and necrosis of cortical neurons from MyD88-/-,TRIF mutant and WT mice. Global ischemia: neuronal survival was similar in all 3 groups of mice. Finally, MCAO: infarct volumes were not statistically different among all 3 groups of mice: MyD88-/-, 23.9+/-9.9 mm(3), TRIF mutant, 26.7+/-5.8 mm(3) and WT, 17.9+/-8.4mm(3). These findings show that disruption of MyD88 or TRIF signaling does not confer protection in brain ischemia and suggests the possibility of additional or alternate downstream adaptors during TLR signaling in cerebral ischemia. |
