Dataset Information

B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury.

ABSTRACT: Spinal cord injury (SCI) is a highly debilitating pathology that has irreversible impacts and results in functional loss. We evaluated the anti-inflammatory and immunologic role of antibody-mediated depletion of B cells through the glycoengineered anti-muCD20 antibody (18B12) in an experimental model of spinal cord compression, in vivo and ex vivo. Intraperitoneal 18B12 was administered at a dose of 30 mg/kg, 1 h and 6 h after SCI, and mice were sacrificed 24 h after trauma. We demonstrated, in vivo, that 18B12 slowed severe hindlimb motor dysfunction (Basso Mouse Scale score) and neuronal death by histological evaluation in SCI mice, as well as decreased expression of nuclear factor-kB, inducible nitric oxide synthase, cytokines, and glial fibrillary acidic protein. Also, 18B12 reduced expression of microglia, just as it lowered the expression of B and T lymphocytes. Moreover, in spinal cord organotypic cultures, pretreatment with 18B12 significantly reduced nitric oxide expression and protected cells from cell death [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay]. In this study, we showed that 18B12 treatment reduces the development of inflammation and tissue injury by alteration of the immune system associated with SCI. This study increases the current knowledge that B-cell depletion is able to exert immunomodulating actions in damaged spinal cords.

SUBMITTER: Casili G

PROVIDER: S-EPMC5081113 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury.

Casili Giovanna G Impellizzeri Daniela D Cordaro Marika M Esposito Emanuela E Cuzzocrea Salvatore S

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20161001 4

Spinal cord injury (SCI) is a highly debilitating pathology that has irreversible impacts and results in functional loss. We evaluated the anti-inflammatory and immunologic role of antibody-mediated depletion of B cells through the glycoengineered anti-muCD20 antibody (18B12) in an experimental model of spinal cord compression, in vivo and ex vivo. Intraperitoneal 18B12 was administered at a dose of 30 mg/kg, 1 h and 6 h after SCI, and mice were sacrificed 24 h after trauma. We demonstrated, in ...[more]

PMID: 27215219

Similar Datasets

Project description:Traumatic spinal cord injury (SCI) causes a sudden onset multi-system disease, permanently altering homeostasis with multiple complications. Consequences include aberrant neuronal circuits, multiple organ system dysfunctions, and chronic phenotypes such as neuropathic pain and metabolic syndrome. Reductionist approaches are used to classify SCI patients based on residual neurological function. Still, recovery varies due to interacting variables, including individual biology, comorbidities, complications, therapeutic side effects, and socioeconomic influences for which data integration methods are lacking. Infections, pressure sores, and heterotopic ossification are known recovery modifiers. However, the molecular pathobiology of the disease-modifying factors altering the neurological recovery-chronic syndrome trajectory is mainly unknown, with significant data gaps between intensive early treatment and chronic phases. Changes in organ function such as gut dysbiosis, adrenal dysregulation, fatty liver, muscle loss, and autonomic dysregulation disrupt homeostasis, generating progression-driving allostatic load. Interactions between interdependent systems produce emergent effects, such as resilience, that preclude single mechanism interpretations. Due to many interacting variables in individuals, substantiating the effects of treatments to improve neurological outcomes is difficult. Acute injury outcome predictors, including blood and cerebrospinal fluid biomarkers, neuroimaging signal changes, and autonomic system abnormalities, often do not predict chronic SCI syndrome phenotypes. In systems medicine, network analysis of bioinformatics data is used to derive molecular control modules. To better understand the evolution from acute SCI to chronic SCI multi-system states, we propose a topological phenotype framework integrating bioinformatics, physiological data, and allostatic load tested against accepted established recovery metrics. This form of correlational phenotyping may reveal critical nodal points for intervention to improve recovery trajectories. This study examines the limitations of current classifications of SCI and how these can evolve through systems medicine.

Dataset Information

B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury.

Publications

B-Cell Depletion with CD20 Antibodies as New Approach in the Treatment of Inflammatory and Immunological Events Associated with Spinal Cord Injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets