Gozde Uzunalli1, Seth Herr2, Alexandra M Dieterly1, Riyi Shi2,3, L Tiffany Lyle4,5,6. 1. Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA. 2. Department of Basic Medical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA. 3. Purdue University Weldon School of Biomedical Engineering, West Lafayette, IN, USA. 4. Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA. tiffanylyle@purdue.edu. 5. Center for Cancer Research, Purdue University, West Lafayette, IN, USA. tiffanylyle@purdue.edu. 6. Center for Comparative Translational Research, Purdue University, West Lafayette, IN, USA. tiffanylyle@purdue.edu.
Abstract
BACKGROUND: Blast-induced traumatic brain injury (bTBI) is a growing health concern due to the increased use of low-cost improvised explosive devices in modern warfare. Mild blast exposures are common amongst military personnel; however, these women and men typically do not have adequate recovery time from their injuries due to the transient nature of behavioral symptoms. bTBI has been linked to heterogeneous neuropathology, including brain edema, neuronal degeneration and cognitive abnormalities depending on the intensity of blast overpressure and frequency. Recent studies have reported heterogeneity in blood-brain barrier (BBB) permeability following blast injury. There still remains a limited understanding of the pathologic changes in the BBB following primary blast injuries. In this study, our goal was to elucidate the pathologic pattern of BBB damage through structural analysis following single and repetitive blast injury using a clinically relevant rat model of bTBI. METHODS: A validated, open-ended shock tube model was used to deliver single or repetitive primary blast waves. The pathology of the BBB was assessed using immunofluorescence and immunohistochemistry assays. All data were analyzed using the one-way ANOVA test. RESULTS: We have demonstrated that exposure to repetitive blast injury affects the desmin-positive and CD13-positive subpopulations of pericytes in the BBB. Changes in astrocytes and microglia were also detected. CONCLUSION: This study provides analysis of the BBB components after repetitive blast injury. These results will be critical as preventative and therapeutic strategies are established for veterans recovering from blast-induced traumatic brain injury.
BACKGROUND:Blast-induced traumatic brain injury (bTBI) is a growing health concern due to the increased use of low-cost improvised explosive devices in modern warfare. Mild blast exposures are common amongst military personnel; however, these women and men typically do not have adequate recovery time from their injuries due to the transient nature of behavioral symptoms. bTBI has been linked to heterogeneous neuropathology, including brain edema, neuronal degeneration and cognitive abnormalities depending on the intensity of blast overpressure and frequency. Recent studies have reported heterogeneity in blood-brain barrier (BBB) permeability following blast injury. There still remains a limited understanding of the pathologic changes in the BBB following primary blast injuries. In this study, our goal was to elucidate the pathologic pattern of BBB damage through structural analysis following single and repetitive blast injury using a clinically relevant rat model of bTBI. METHODS: A validated, open-ended shock tube model was used to deliver single or repetitive primary blast waves. The pathology of the BBB was assessed using immunofluorescence and immunohistochemistry assays. All data were analyzed using the one-way ANOVA test. RESULTS: We have demonstrated that exposure to repetitive blast injury affects the desmin-positive and CD13-positive subpopulations of pericytes in the BBB. Changes in astrocytes and microglia were also detected. CONCLUSION: This study provides analysis of the BBB components after repetitive blast injury. These results will be critical as preventative and therapeutic strategies are established for veterans recovering from blast-induced traumatic brain injury.
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Authors: Gozde Uzunalli; Alexandra M Dieterly; Chinyere M Kemet; Hsin-Yi Weng; Arvin H Soepriatna; Craig J Goergen; Aparna B Shinde; Michael K Wendt; L Tiffany Lyle Journal: Oncotarget Date: 2019-10-29