An imaging technique lets scientists peer through the skin of a whole mouse or rat to examine its organs after death. Ali Ertürk of the Ludwig Maximilians University of Munich in Germany and his colleagues created a technique called ultimate DISCO (uDISCO), which removes pigments and lipids from the tissues of dead animals using an organic solvent. This leaves the organs and skin intact but transparent, while preserving genetically encoded fluorescent proteins. The method revealed the nervous system of a mouse in stark detail. uDISCO also shrinks bodies by up to 65%, making it possible to image whole animals using light-sheet microscopy, which excels at imaging smaller samples. Nature Methods http://dx.

Coding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with late onset Alzheimer’s disease (AD). We demonstrate that amyloid plaque seeding is increased in the absence of functional Trem2. Increased seeding is accompanied by decreased microglial clustering around newly seeded plaques and reduced plaque associated Apolipoprotein E (ApoE). Reduced ApoE deposition in plaques is also observed in brains of AD patients carrying TREM2 coding variants. Proteomic analyses and microglia depletion experiments revealed microglia as one origin of plaque associated ApoE. Longitudinal amyloid small animal positron emission tomography demonstrates accelerated amyloidogenesis in Trem2 loss of function mutants at early stages, which progressed at a lower rate with aging. These findings suggest that in the absence of functional Trem2 early amyloidogenesis is accelerated due to reduced phagocytic clearance of amyloid seeds despite reduced plaque associated ApoE.

Analysis of entire transparent rodent bodies after clearing could provide holistic biological information in health and disease, but reliable imaging and quantification of fluorescent protein signals deep inside the tissues remained a challenge. Here, we developed vDISCO, a pressure driven, nanobody based whole-body immunolabeling technology to enhance the signal of fluorescent proteins by up to two orders of magnitude. This allowed us to image and quantify subcellular details through bones, skin and highly autofluorescent tissues of intact transparent mice. For the first time, we visualized whole-body neuronal projections in adult mice. We assessed CNS trauma effects in the whole-body and found degeneration of peripheral nerve terminals in the torso. Furthermore, vDISCO revealed short vascular connections between skull marrow and brain meninges, which were filled with immune cells upon stroke. Thus, our new approach enables unbiased comprehensive studies of the interactions between the nervous system and the rest of the body.

Highlights d DeepMACT is a deep learning-based pipeline for comprehensive analysis of metastases d DeepMACT identifies micrometastases and single cancer cells in full-body 3D scans d DeepMACT reveals the efficacy of antibody-drug targeting in the entire body d DeepMACT indicates that the tumor microenvironment affects drug targeting efficacy

Neuroinflammation contributes substantially to stroke pathophysiology. Cerebral invasion of peripheral leukocytes-particularly T cells-has been shown to be a key event promoting inflammatory tissue damage after stroke. While previous research has focused on the vascular invasion of T cells into the ischemic brain, the choroid plexus (ChP) as an alternative cerebral T-cell invasion route after stroke has not been investigated. We here report specific accumulation of T cells in the peri-infarct cortex and detection of T cells as the predominant population in the ipsilateral ChP in mice as well as in human post-stroke autopsy samples. T-cell migration from the ChP to the peri-infarct cortex was confirmed by in vivo cell tracking of photoactivated T cells. In turn, significantly less T cells invaded the ischemic brain after photothrombotic lesion of the ipsilateral ChP and in a stroke model encompassing ChP ischemia. We detected a gradient of CCR2 ligands as the potential driving force and characterized the neuroanatomical pathway for the intracerebral migration. In summary, our study demonstrates that the ChP is a key invasion route for post-stroke cerebral T-cell invasion and describes a CCR2-ligand gradient between cortex and ChP as the potential driving mechanism for this invasion route.