Skin Wound following Irradiation Aggravates Radiation-Induced Brain Injury in a Mouse Model
Radiation injury- and radiation combined with skin injury-induced inflammatory responses in the mouse brain were evaluated in this study. Female B6D2F1/J mice were subjected to a sham, a skin wound (SW), 9.5 Gy <sup>60</sup>Co total-body gamma irradiation (RI), or 9.5 Gy RI combined with...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/10701 |
| _version_ | 1797591591709310976 |
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| author | Mang Xiao Xianghong Li Li Wang Bin Lin Min Zhai Lisa Hull Alex Zizzo Wanchang Cui Juliann G. Kiang |
| author_facet | Mang Xiao Xianghong Li Li Wang Bin Lin Min Zhai Lisa Hull Alex Zizzo Wanchang Cui Juliann G. Kiang |
| author_sort | Mang Xiao |
| collection | DOAJ |
| description | Radiation injury- and radiation combined with skin injury-induced inflammatory responses in the mouse brain were evaluated in this study. Female B6D2F1/J mice were subjected to a sham, a skin wound (SW), 9.5 Gy <sup>60</sup>Co total-body gamma irradiation (RI), or 9.5 Gy RI combined with a skin puncture wound (RCI). Survival, body weight, and wound healing were tracked for 30 days, and mouse brain samples were collected on day 30 after SW, RI, RCI, and the sham control. Our results showed that RCI caused more severe animal death and body weight loss compared with RI, and skin wound healing was significantly delayed by RCI compared to SW. RCI and RI increased the chemokines Eotaxin, IP-10, MIG, 6Ckine/Exodus2, MCP-5, and TIMP-1 in the brain compared to SW and the sham control mice, and the Western blot results showed that IP-10 and p21 were significantly upregulated in brain cells post-RI or -RCI. RI and RCI activated both astrocytes and endothelial cells in the mouse brain, subsequently inducing blood–brain barrier (BBB) leakage, as shown by the increased ICAM1 and GFAP proteins in the brain and GFAP in the serum. The Doublecortin (DCX) protein, the “gold standard” for measuring neurogenesis, was significantly downregulated by RI and RCI compared with the sham group. Furthermore, RI and RCI decreased the expression of the neural stem cell marker E-cadherin, the intermediate progenitor marker MASH1, the immature neuron cell marker NeuroD1, and the mature neuron cell marker NeuN, indicating neural cell damage in all development stages after RI and RCI. Immunohistochemistry (IHC) staining further confirmed the significant loss of neural cells in RCI. Our data demonstrated that RI and RCI induced brain injury through inflammatory pathways, and RCI exacerbated neural cell damage more than RI. |
| first_indexed | 2024-03-11T01:40:33Z |
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| id | doaj.art-ee38a05dd27443b98a1d0fb987b6ec6b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:40:33Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ee38a05dd27443b98a1d0fb987b6ec6b2023-11-18T16:42:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131070110.3390/ijms241310701Skin Wound following Irradiation Aggravates Radiation-Induced Brain Injury in a Mouse ModelMang Xiao0Xianghong Li1Li Wang2Bin Lin3Min Zhai4Lisa Hull5Alex Zizzo6Wanchang Cui7Juliann G. Kiang8Scientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USAScientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USAScientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USAScientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USAScientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USAScientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USAScientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USAScientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USAScientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, USARadiation injury- and radiation combined with skin injury-induced inflammatory responses in the mouse brain were evaluated in this study. Female B6D2F1/J mice were subjected to a sham, a skin wound (SW), 9.5 Gy <sup>60</sup>Co total-body gamma irradiation (RI), or 9.5 Gy RI combined with a skin puncture wound (RCI). Survival, body weight, and wound healing were tracked for 30 days, and mouse brain samples were collected on day 30 after SW, RI, RCI, and the sham control. Our results showed that RCI caused more severe animal death and body weight loss compared with RI, and skin wound healing was significantly delayed by RCI compared to SW. RCI and RI increased the chemokines Eotaxin, IP-10, MIG, 6Ckine/Exodus2, MCP-5, and TIMP-1 in the brain compared to SW and the sham control mice, and the Western blot results showed that IP-10 and p21 were significantly upregulated in brain cells post-RI or -RCI. RI and RCI activated both astrocytes and endothelial cells in the mouse brain, subsequently inducing blood–brain barrier (BBB) leakage, as shown by the increased ICAM1 and GFAP proteins in the brain and GFAP in the serum. The Doublecortin (DCX) protein, the “gold standard” for measuring neurogenesis, was significantly downregulated by RI and RCI compared with the sham group. Furthermore, RI and RCI decreased the expression of the neural stem cell marker E-cadherin, the intermediate progenitor marker MASH1, the immature neuron cell marker NeuroD1, and the mature neuron cell marker NeuN, indicating neural cell damage in all development stages after RI and RCI. Immunohistochemistry (IHC) staining further confirmed the significant loss of neural cells in RCI. Our data demonstrated that RI and RCI induced brain injury through inflammatory pathways, and RCI exacerbated neural cell damage more than RI.https://www.mdpi.com/1422-0067/24/13/10701radiationskin woundradiation combined injuryinflammationbrain injuryblood–brain barrier leakage |
| spellingShingle | Mang Xiao Xianghong Li Li Wang Bin Lin Min Zhai Lisa Hull Alex Zizzo Wanchang Cui Juliann G. Kiang Skin Wound following Irradiation Aggravates Radiation-Induced Brain Injury in a Mouse Model International Journal of Molecular Sciences radiation skin wound radiation combined injury inflammation brain injury blood–brain barrier leakage |
| title | Skin Wound following Irradiation Aggravates Radiation-Induced Brain Injury in a Mouse Model |
| title_full | Skin Wound following Irradiation Aggravates Radiation-Induced Brain Injury in a Mouse Model |
| title_fullStr | Skin Wound following Irradiation Aggravates Radiation-Induced Brain Injury in a Mouse Model |
| title_full_unstemmed | Skin Wound following Irradiation Aggravates Radiation-Induced Brain Injury in a Mouse Model |
| title_short | Skin Wound following Irradiation Aggravates Radiation-Induced Brain Injury in a Mouse Model |
| title_sort | skin wound following irradiation aggravates radiation induced brain injury in a mouse model |
| topic | radiation skin wound radiation combined injury inflammation brain injury blood–brain barrier leakage |
| url | https://www.mdpi.com/1422-0067/24/13/10701 |
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