Tlr2 Deficiency is Associated with Enhanced Elements of Neuronal Repair and Caspase 3 Activation Following Brain Ischemia

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.