Sex Does Not Influence Visual Outcomes After Blast-Mediated Traumatic Brain Injury but IL-1 Pathway Mutations Confer Partial Rescue
| Autor: | Alexander G. Bassuk, Abhigna Akurathi, Elizabeth A. Newell, Brittany P. Todd, Elliot Burghardt, Lucy P. Evans, Matthew M. Harper, Laura M. Dutca, Nickolas Boehme, Vinit B. Mahajan, Shu Wu, Polly J. Ferguson |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Retinal Ganglion Cells Traumatic brain injury Cell Survival Visual Acuity Poison control blast medicine.disease_cause Retina Andrology 03 medical and health sciences Mice 0302 clinical medicine Sex Factors Blast Injuries Brain Injuries Traumatic TBI medicine Electroretinography visual function Animals sex Mice Knockout Mutation Transcription Factor Brn-3A business.industry IL-1 Interleukin medicine.disease Immunohistochemistry Blockade Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Retinal ganglion cell Gene Expression Regulation Knockout mouse Female business 030217 neurology & neurosurgery Tomography Optical Coherence Interleukin-1 |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 |
| Popis: | Purpose In a mouse model of blast-mediated traumatic brain injury (bTBI), interleukin-1 (IL-1)-pathway components were tested as potential therapeutic targets for bTBI-mediated retinal ganglion cell (RGC) dysfunction. Sex was also evaluated as a variable for RGC outcomes post-bTBI. Methods Male and female mice with null mutations in genes encoding IL-1α, IL-1β, or IL-1RI were compared to C57BL/6J wild-type (WT) mice after exposure to three 20-psi blast waves given at an interblast interval of 1 hour or to mice receiving sham injury. To determine if genetic blockade of IL-1α, IL-1β, or IL-1RI could prevent damage to RGCs, the function and structure of these cells were evaluated by pattern electroretinogram and optical coherence tomography, respectively, 5 weeks following blast or sham exposure. RGC survival was also quantitatively assessed via immunohistochemical staining of BRN3A at the completion of the study. Results Our results showed that male and female WT mice had a similar response to blast-induced retinal injury. Generally, constitutive deletion of IL-1α, IL-1β, or IL-1RI did not provide full protection from the effects of bTBI on visual outcomes; however, injured WT mice had significantly worse visual outcomes compared to the injured genetic knockout mice. Conclusions Sex does not affect RGC outcomes after bTBI. The genetic studies suggest that deletion of these IL-1 pathway components confers some protection, but global deletion from birth did not result in a complete rescue. |
| Databáze: | OpenAIRE |
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