| First Author | Schanbacher C | Year | 2022 |
| Journal | Int J Mol Sci | Volume | 23 |
| Issue | 2 | PubMed ID | 35054890 |
| Mgi Jnum | J:318849 | Mgi Id | MGI:6861153 |
| Doi | 10.3390/ijms23020706 | Citation | Schanbacher C, et al. (2022) ERK1/2 Activity Is Critical for the Outcome of Ischemic Stroke. Int J Mol Sci 23(2) |
| abstractText | Ischemic disorders are the leading cause of death worldwide. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are thought to affect the outcome of ischemic stroke. However, it is under debate whether activation or inhibition of ERK1/2 is beneficial. In this study, we report that the ubiquitous overexpression of wild-type ERK2 in mice (ERK2(wt)) is detrimental after transient occlusion of the middle cerebral artery (tMCAO), as it led to a massive increase in infarct volume and neurological deficits by increasing blood-brain barrier (BBB) leakiness, inflammation, and the number of apoptotic neurons. To compare ERK1/2 activation and inhibition side-by-side, we also used mice with ubiquitous overexpression of the Raf-kinase inhibitor protein (RKIP(wt)) and its phosphorylation-deficient mutant RKIP(S153A), known inhibitors of the ERK1/2 signaling cascade. RKIP(wt) and RKIP(S153A) attenuated ischemia-induced damages, in particular via anti-inflammatory signaling. Taken together, our data suggest that stimulation of the Raf/MEK/ERK1/2-cascade is severely detrimental and its inhibition is rather protective. Thus, a tight control of the ERK1/2 signaling is essential for the outcome in response to ischemic stroke. |
