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TitleTlr2 Deficiency is Associated with Enhanced Elements of Neuronal Repair and Caspase 3 Activation Following Brain Ischemia.
Publication TypeJournal Article
Year of Publication2019
AuthorsGorup, Dunja, Siniša Škokić, Jasna Kriz, and Srećko Gajović
JournalSci Rep
Volume9
Issue1
Pagination2821
Date Published2019 Feb 26
ISSN2045-2322
Abstract

The aim of this study was to apply multimodal in vivo imaging to assess the influence of altered innate immunity on brain repair after ischemic lesion. Tlr2-deficient mice were compared to wild type controls, as they lack Tlr2-mediated pro-inflammatory signaling triggered by postischemic necrosis. The ischemic lesion was induced by transient middle cerebral artery occlusion for 60 min, followed by brain imaging and analysis at four time points until 28 days after ischemia. Multimodal in vivo imaging involved a combination of 3 modalities: (1) magnetic resonance imaging by T2-weighted scans to assess brain lesion size, (2) bioluminescence imaging of Gap43-luc/gfp transgenic mice to visualize the axonal remodeling, and (3) caged-luciferin bioluminescence imaging of DEVD-luciferin allowing for visualization of caspase 3 and 7 activity in Gap43-luc/gfp mice. This enabled innovative correlation of the MRI-determined lesion size to photon fluxes obtained by bioluminescence imaging. Our data revealed that following ischemia, Tlr2-deficient mice had higher Gap43 expression and higher levels of caspases 3 and 7 activity, which was accompanied by enhanced levels of synaptic plasticity markers DLG4 and synaptophysin when compared to wild type controls. Altered inflammation in Tlr2-deficient mice was accompanied by enhanced elements of post-stroke repair, in particular during the chronic phase of recovery, but also with delayed final consolidation of the brain lesion.

DOI10.1038/s41598-019-39541-3
Alternate JournalSci Rep
PubMed ID30808918
PubMed Central IDPMC6391535
Grant ListIP-06-2016-1892 / / Hrvatska Zaklada za Znanost (Croatian Science Foundation) /
REGPOT–2012–CT2012–316120 / / EC | Seventh Framework Programme (EC Seventh Framework Programme) /