Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury
| Autor: | María José Bellini, Macarena Lorena Herrera, Claudia B. Hereñú, Sandra Bandín, Leandro Gabriel Champarini |
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| Přispěvatelé: | Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Agencia Nacional de Promoción Científica y Tecnológica (Argentina) |
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Traumatic brain injury Genetic enhancement Genetic Vectors Neuroprotection Injections Intramuscular Glial scar Neuroinflammation Internal medicine Brain Injuries Traumatic Glial Fibrillary Acidic Protein medicine Animals Humans Vimentin Gliosis Insulin-Like Growth Factor I Microglia Glial fibrillary acidic protein biology business.industry General Neuroscience Calcium-Binding Proteins Microfilament Proteins Genetic Therapy medicine.disease Rats medicine.anatomical_structure Endocrinology Memory Short-Term Treatment Outcome Cerebral cortex Astrocytes biology.protein IGF-1 business Neuroglia Psychomotor Performance |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Reactive gliosis is a key feature and an important pathophysiological mechanism underlying chronic neurodegeneration following traumatic brain injury (TBI). In this study, we have explored the effects of intramuscular IGF-1 gene therapy on reactive gliosis and functional outcome after an injury of the cerebral cortex. Young adult male rats were intramuscularly injected with a recombinant adenoviral construct harboring the cDNA of human IGF-1 (RAd-IGF1), with a control vector expressing green fluorescent protein (RAd-GFP) or PBS as control. Three weeks after the intramuscular injections of adenoviral vectors, animals were subjected to a unilateral penetrating brain injury. The data revealed that RAd-IGF1 gene therapy significantly increased serum IGF1 levels and improved working memory performance after one week of TBI as compared to PBS or RAd-GFP lesioned animals. At the same time, when we analyzed the effects of therapy on glial scar formation, the treatment with RAd-IGF1 did not modify the number of glial fibrillary acidic protein (GFAP) positive cells, but we observed a decrease in vimentin immunoreactive astrocytes at 7 days post-lesion in the injured hemisphere compared to RAd-GFP group. Moreover, IGF-1 gene therapy reduced the number of Iba1+ cells with reactive phenotype and the number of MHCII + cells in the injured hemisphere. These results suggest that intramuscular IGF-1 gene therapy may represent a new approach to prevent traumatic brain injury outcomes in rats. This research was funded by grant PIP 0618 from CONICET, Argentina to MJB and by grant PICT-2018-02446 Plan Argentina Innovadora from Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación to CBH. |
| Databáze: | OpenAIRE |
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