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Multiple sclerosis (MS) is a complex autoimmune and neurodegenerative disorder that affects the central nervous system (CNS). It is characterized by a heterogeneous disease course involving demyelination and inflammation. In this study, we utilized two distinct animal models, cuprizone (CPZ)-induced demyelination and experimental autoimmune encephalomyelitis (EAE), to replicate various aspects of the disease. We aimed to investigate the differential CNS responses by examining the proteomic profiles of EAE mice during the peak disease (15 days post-induction) and cuprizone-fed mice during the acute phase (38 days). Specifically, we focused on two different regions of the CNS: the dorsal cortex (Cx) and the entire spinal cord (SC). Our findings revealed varied glial, synaptic, dendritic, mitochondrial, and inflammatory responses within these regions for each model. Notably, we identified a single protein, Orosomucoid-1 (Orm1), also known as Alpha-1-acid glycoprotein 1 (AGP1), that consistently exhibited alterations in both models and regions. This study provides insights into the similarities and differences in the responses of these regions in two distinct demyelinating models., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) and central nervous system primitive neuroectodermal tumors (CNS-PNET) are pediatric brain tumors with poor survival and life-long negative side effects. Here, the aim was to characterize the efficacy and safety of the oncolytic adenovirus, Delta-24-RGD, which selectively replicates in and kills tumor cells., Experimental Design: Delta-24-RGD determinants for infection and replication were evaluated in patient expression datasets. Viral replication and cytotoxicity were assessed in vitro in a battery of CNS-PNET and AT/RT cell lines. In vivo , efficacy was determined in different orthotopic mouse models, including early and established tumor models, a disseminated AT/RT lesion model, and immunocompetent humanized mouse models (hCD34 + -NSG-SGM3)., Results: Delta-24-RGD infected and replicated efficiently in all the cell lines tested. In addition, the virus induced dose-dependent cytotoxicity [IC 50 value below 1 plaque-forming unit (PFU)/cell] and the release of immunogenic markers. In vivo , a single intratumoral Delta-24-RGD injection (10 7 or 10 8 PFU) significantly increased survival and led to long-term survival in AT/RT and PNET models. Delta-24-RGD hindered the dissemination of AT/RTs and increased survival, leading to 70% of long-term survivors. Of relevance, viral administration to established tumor masses (30 days after engraftment) showed therapeutic benefit. In humanized immunocompetent models, Delta-24-RGD significantly extended the survival of mice bearing AT/RTs or PNETs (ranging from 11 to 27 days) and did not display any toxicity associated with inflammation. Immunophenotyping of Delta-24-RGD-treated tumors revealed increased CD8 + T-cell infiltration., Conclusions: Delta-24-RGD is a feasible therapeutic option for AT/RTs and CNS-PNETs. This work constitutes the basis for potential translation to the clinical setting., (©2020 American Association for Cancer Research.)

Imaging of small laboratory animals in clinical MRI scanners is feasible but challenging. Compared with dedicated preclinical systems, clinical scanners have relatively low B 0 field (1.5-3.0 T) and gradient strength (40-60 mT/m). This work explored the use of wireless inductively coupled coils (ICCs) combined with appropriate pulse sequence parameters to overcome these two drawbacks, with a special emphasis on the optimization of the coil passive detuning circuit for this application. A Bengal rose photothrombotic stroke model was used to induce cortical infarction in rats and mice. Animals were imaged in a 3T scanner using T2 and T1-weighted sequences. In all animals, the ICCs allowed acquisition of high-quality images of the infarcted brain at acute and chronic stages. Images obtained with the ICCs showed a substantial increase in SNR compared to clinical coils (by factors of 6 in the rat brain and 16-17 in the mouse brain), and the absence of wires made the animal preparation workflow straightforward.

Tumor-induced immunosuppression is a common obstacle for cancer treatment. Adrenergic signaling triggered by chronic stress participates in the creation of an immunosuppressive microenvironment by promoting myeloid-derived suppressor cell (MDSC) proliferation and activation. In this issue of the JCI, Mohammadpour et al. elegantly delve into the mechanisms underlying MDSC contribution to tumor development. They used in vitro and in vivo mouse models to demonstrate that chronic stress results in MDSC accumulation, survival, and immune-inhibitory activity. Of therapeutic relevance, the authors showed that propranolol, a commonly prescribed β-blocker, can reduce MDSC immunosuppression and enhance the effect of other cancer therapies.