Reactive Astrocytes Protect Tissue and Preserve Function after Spinal Cord Injury
| Autor: | Ngan B. Doan, Michael V. Sofroniew, Michael J. Woo, Keith E. Tansey, Jill R. Faulkner, Julia E. Herrmann |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Genetically modified mouse
Pathology medicine.medical_specialty Nerve Crush Recombinant Fusion Proteins Transgene Development/Plasticity/Repair Mice Transgenic Wounds Stab Motor Activity Biology Antiviral Agents Thymidine Kinase Glial scar Mice Glial Fibrillary Acidic Protein medicine Animals Transgenes Ganciclovir Spinal cord injury Spinal Cord Injuries Inflammation Neurons General Neuroscience Recovery of Function medicine.disease Oligodendrocyte Mice Inbred C57BL Tissue Degeneration Disease Models Animal Oligodendroglia medicine.anatomical_structure Bromodeoxyuridine Blood-Brain Barrier Astrocytes Disease Progression Crush injury Infiltration (medical) Neuroscience Cell Division |
| Zdroj: | The Journal of Neuroscience. 24:2143-2155 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | Reactive astrocytes are prominent in the cellular response to spinal cord injury (SCI), but their roles are not well understood. We used a transgenic mouse model to study the consequences of selective and conditional ablation of reactive astrocytes after stab or crush SCI. Mice expressing a glial fibrillary acid protein-herpes simplex virus-thymidine kinase transgene were given mild or moderate SCI and treated with the antiviral agent ganciclovir (GCV) to ablate dividing, reactive, transgene-expressing astrocytes in the immediate vicinity of the SCI. Small stab injuries in control mice caused little tissue disruption, little demyelination, no obvious neuronal death, and mild, reversible functional impairments. Equivalent small stab injuries in transgenic mice given GCV to ablate reactive astrocytes caused failure of blood-brain barrier repair, leukocyte infiltration, local tissue disruption, severe demyelination, neuronal and oligodendrocyte death, and pronounced motor deficits. Moderate crush injuries in control mice caused focal tissue disruption and cellular degeneration, with moderate, primarily reversible motor impairments. Equivalent moderate crush injuries combined with ablation of reactive astrocytes caused widespread tissue disruption, pronounced cellular degeneration, and failure of wound contraction, with severe persisting motor deficits. These findings show that reactive astrocytes provide essential activities that protect tissue and preserve function after mild or moderate SCI. In nontransgenic animals, crush or contusion SCIs routinely exhibit regions of degenerated tissue that are devoid of astrocytes. Our findings suggest that identifying ways to preserve reactive astrocytes, to augment their protective functions, or both, may lead to novel approaches to reducing secondary tissue degeneration and improving functional outcome after SCI. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|