S100B inhibition reduces behavioral and pathologic changes in experimental traumatic brain injury
| Autor: | Kara B Duffy, Lauriaselle Afanador, Danna B. Zimmer, Bogdan A. Stoica, Alan I. Faden, David J. Loane, Shruti V. Kabadi |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Lipopolysaccharides
Male Traumatic brain injury Receptor for Advanced Glycation End Products S100 Calcium Binding Protein beta Subunit Neuroprotection Cell Line Interferon-gamma Mice Memory medicine Animals Interferon gamma Neutralizing antibody Postural Balance Neuroinflammation Inflammation Mice Knockout biology Microglia Behavior Animal business.industry Neurodegeneration Brain Recognition Psychology Macrophage Activation medicine.disease Antibodies Neutralizing Mice Inbred C57BL medicine.anatomical_structure Neurology Brain Injuries Knockout mouse biology.protein Original Article Neurology (clinical) Cardiology and Cardiovascular Medicine business Neuroscience medicine.drug |
| Popis: | Neuroinflammation following traumatic brain injury (TBI) is increasingly recognized to contribute to chronic tissue loss and neurologic dysfunction. Circulating levels of S100B increase after TBI and have been used as a biomarker. S100B is produced by activated astrocytes and can promote microglial activation; signaling by S100B through interaction with the multiligand advanced glycation end product-specific receptor (AGER) has been implicated in brain injury and microglial activation during chronic neurodegeneration. We examined the effects of S100B inhibition in a controlled cortical impact model, using S100B knockout mice or administration of neutralizing S100B antibody. Both interventions significantly reduced TBI-induced lesion volume, improved retention memory function, and attenuated microglial activation. The neutralizing antibody also significantly reduced sensorimotor deficits and improved neuronal survival in the cortex. However, S100B did not alter microglial activation in BV2 cells or primary microglial cultures stimulated by lipopolysaccharide or interferon gamma. Further, proximity ligation assays did not support direct interaction in the brain between S100B and AGER following TBI. Future studies are needed to elucidate specific pathways underlying S100B-mediated neuroinflammatory actions after TBI. Our results strongly implicate S100B in TBI-induced neuroinflammation, cell loss, and neurologic dysfunction, thereby indicating that it is a potential therapeutic target for TBI. |
| Databáze: | OpenAIRE |
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