Recent Neuropathology Concepts.

The last session of the 2024 European Society of Toxicologic Pathology Congress was dedicated to recent neuro concepts, encompassing various topics including artificial intelligence (AI) applied to toxicologic pathology, new technologies for visualization and/or analysis of tissues, as well as specific case reports. Four presentations detailed the role of AI and computational pathology for toxicologic pathologists, usage of cryofluorescent tomography in neuropathology, blood-brain barrier organoids in early drug screening, and spatial transcriptomics in toxicologic pathology. In addition, there were two short presentations about a spontaneous brain lesion in Beagle dogs as well as central nervous system lesions related to adeno-associated virus vectors administration in various preclinical species.

Advanced tissue technologies of blood-brain barrier organoids as high throughput toxicity readouts in drug development.

Recent advancements in engineering Complex models (CIVMs) such as Blood-brain barrier (BBB) organoids offer promising platforms for preclinical drug testing. However, their application in drug development, and especially for the regulatory purposes of toxicity assessment, requires robust and reproducible techniques. Here, we developed an adapted set of orthogonal image-based tissue methods including hematoxylin and eosin staining (HE), immunohistochemistry (IHC), multiplex immunofluorescence (mIF), and Matrix Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) to validate CIVMs for drug toxicity assessments.

Complex In Vitro Model Characterization for Context of Use in Toxicologic Pathology: Use Cases by Collaborative Teams of Biologists, Bioengineers, and Pathologists.

Complex in vitro models (CIVMs) offer the potential to increase the clinical relevance of preclinical efficacy and toxicity assessments and reduce the reliance on animals in drug development. The European Society of Toxicologic Pathology (ESTP) and Society for Toxicologic Pathology (STP) are collaborating to highlight the role of pathologists in the development and use of CIVM. Pathologists are trained in comparative animal medicine which enhances their understanding of mechanisms of human and animal diseases, thus allowing them to bridge between animal models and humans.

Rapid and Efficient Gene Editing for Direct Transplantation of Naive Murine Cas9 T Cells.

Gene editing of primary T cells is a difficult task. However, it is important for research and especially for clinical T-cell transfers. CRISPR/Cas9 is the most powerful gene-editing technique.

Bone marrow-derived myeloid progenitors in the leptomeninges of adult mice.

Although the bone marrow contains most hematopoietic activity during adulthood, hematopoietic stem and progenitor cells can be recovered from various extramedullary sites. Cells with hematopoietic progenitor properties have even been reported in the adult brain under steady-state conditions, but their nature and localization remain insufficiently defined. Here, we describe a heterogeneous population of myeloid progenitors in the leptomeninges of adult C57BL/6 mice.

Lymphoid Aggregates in the CNS of Progressive Multiple Sclerosis Patients Lack Regulatory T Cells.

In gray matter pathology of multiple sclerosis, neurodegeneration associates with a high degree of meningeal inflammatory activity. Importantly, ectopic lymphoid follicles (eLFs) were identified at the inflamed meninges of patients with progressive multiple sclerosis. Besides T lymphocytes, they comprise B cells and might elicit germinal center (GC)-like reactions.

The mere physical presence of another person reduces human autonomic responses to aversive sounds.

Social animals show reduced physiological responses to aversive events if a conspecific is physically present. Although humans are innately social, it is unclear whether the mere physical presence of another person is sufficient to reduce human autonomic responses to aversive events. In our study, participants experienced aversive and neutral sounds alone (alone treatment) or with an unknown person that was physically present without providing active support.

Characterization of blood-brain barrier integrity in a B-cell-dependent mouse model of multiple sclerosis.

Recent studies with B-cell-depleting antibodies have demonstrated clinical success in the treatment of multiple sclerosis (MS) patients. While these antibodies efficiently target B cells in the blood, it is unclear how effective they are in the central nervous system (CNS), especially in the context of limited blood-brain barrier (BBB) permeability and the ongoing discussion on the relevance of B-cell aggregate formation in the brains of SP-MS patients. The aim of this study was to evaluate BBB integrity in the context of B-cell-dependent neuroinflammation in a mouse model of MS.