Reactive astrocyte-derived neurotoxicity is mitigated by vitronectin in traumatic brain injury mouse model
Vitronectin (VN) is an extracellular matrix protein that contributes to brain injury repair by regulating the fibrinolytic system. VN interacts with glial cells to regulate cytokine production. However, it is unclear how VN affects glial dynamics to promote repair of brain injury in a mouse model of...
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Elsevier
2025-12-01
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| Series: | IBRO Neuroscience Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667242125001083 |
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| author | Minori Yamashita Nito Nakahira Kei Hashimoto Hirono Kobayashi Mari Nakashima Hiroko Ikeshima-Kataoka Yasunori Miyamoto |
| author_facet | Minori Yamashita Nito Nakahira Kei Hashimoto Hirono Kobayashi Mari Nakashima Hiroko Ikeshima-Kataoka Yasunori Miyamoto |
| author_sort | Minori Yamashita |
| collection | DOAJ |
| description | Vitronectin (VN) is an extracellular matrix protein that contributes to brain injury repair by regulating the fibrinolytic system. VN interacts with glial cells to regulate cytokine production. However, it is unclear how VN affects glial dynamics to promote repair of brain injury in a mouse model of traumatic brain injury (TBI). Here, we examined the effect of VN on astrocyte dynamics and neuronal cell death in mouse cerebral cortices after stab wounds. First, we verified that Vn-/- cortices with stab wound surgery showed severe neuronal cell death and astrocyte activation around the lesion. In addition, the concentration of complement C3 was increased in Vn-/- cortices after the stab wound, which was co-localized with astrocytes, suggesting that VN regulates astrocyte-derived C3 secretion and attenuates neurodegeneration after TBI. To further examine this, we collected secretions from VN-treated primary astrocytes and added them to primary cortical neurons, and found that secretions from VN-treated astrocytes have low neurotoxicity. Because the secretion from VN-treated astrocytes contained high levels of C3, we treated primary cortical neurons with the secretion from astrocytes and an inhibitor of the complement pathway, CD59, and analyzed neuronal cell death; results showed that inhibition of the complement pathway attenuates astrocyte secretion-induced neuronal apoptosis. Our results indicate that VN exerts a neuroprotective function through the suppression of C3 secretion from astrocytes. Therefore, VN plays a role in mitigating neurodegeneration after TBI by suppressing complement C3 secretion from reactive astrocytes. |
| format | Article |
| id | doaj-art-ecabdf26dae941f58ccbcb2fe4dcb10a |
| institution | Matheson Library |
| issn | 2667-2421 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | IBRO Neuroscience Reports |
| spelling | doaj-art-ecabdf26dae941f58ccbcb2fe4dcb10a2025-07-26T05:24:35ZengElsevierIBRO Neuroscience Reports2667-24212025-12-0119300306Reactive astrocyte-derived neurotoxicity is mitigated by vitronectin in traumatic brain injury mouse modelMinori Yamashita0Nito Nakahira1Kei Hashimoto2Hirono Kobayashi3Mari Nakashima4Hiroko Ikeshima-Kataoka5Yasunori Miyamoto6Graduate School of Humanities and Sciences, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, JapanGraduate School of Humanities and Sciences, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, JapanInstitute for Human Life Science, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, JapanDepartment of Biology, Faculty of Science, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, JapanGraduate School of Humanities and Sciences, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, JapanKitasato University School of Frontier Engineering, Sagamihara, Kanagawa, JapanGraduate School of Humanities and Sciences, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan; Institute for Human Life Science, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan; Department of Biology, Faculty of Science, Ochanomizu University, Ohtsuka, Bunkyo-ku, Tokyo, Japan; Correspondence to: Institute for Human Life Science, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, Japan.Vitronectin (VN) is an extracellular matrix protein that contributes to brain injury repair by regulating the fibrinolytic system. VN interacts with glial cells to regulate cytokine production. However, it is unclear how VN affects glial dynamics to promote repair of brain injury in a mouse model of traumatic brain injury (TBI). Here, we examined the effect of VN on astrocyte dynamics and neuronal cell death in mouse cerebral cortices after stab wounds. First, we verified that Vn-/- cortices with stab wound surgery showed severe neuronal cell death and astrocyte activation around the lesion. In addition, the concentration of complement C3 was increased in Vn-/- cortices after the stab wound, which was co-localized with astrocytes, suggesting that VN regulates astrocyte-derived C3 secretion and attenuates neurodegeneration after TBI. To further examine this, we collected secretions from VN-treated primary astrocytes and added them to primary cortical neurons, and found that secretions from VN-treated astrocytes have low neurotoxicity. Because the secretion from VN-treated astrocytes contained high levels of C3, we treated primary cortical neurons with the secretion from astrocytes and an inhibitor of the complement pathway, CD59, and analyzed neuronal cell death; results showed that inhibition of the complement pathway attenuates astrocyte secretion-induced neuronal apoptosis. Our results indicate that VN exerts a neuroprotective function through the suppression of C3 secretion from astrocytes. Therefore, VN plays a role in mitigating neurodegeneration after TBI by suppressing complement C3 secretion from reactive astrocytes.http://www.sciencedirect.com/science/article/pii/S2667242125001083VitronectinTraumatic brain injuryAstrocyteNeuronal cell deathC3 |
| spellingShingle | Minori Yamashita Nito Nakahira Kei Hashimoto Hirono Kobayashi Mari Nakashima Hiroko Ikeshima-Kataoka Yasunori Miyamoto Reactive astrocyte-derived neurotoxicity is mitigated by vitronectin in traumatic brain injury mouse model IBRO Neuroscience Reports Vitronectin Traumatic brain injury Astrocyte Neuronal cell death C3 |
| title | Reactive astrocyte-derived neurotoxicity is mitigated by vitronectin in traumatic brain injury mouse model |
| title_full | Reactive astrocyte-derived neurotoxicity is mitigated by vitronectin in traumatic brain injury mouse model |
| title_fullStr | Reactive astrocyte-derived neurotoxicity is mitigated by vitronectin in traumatic brain injury mouse model |
| title_full_unstemmed | Reactive astrocyte-derived neurotoxicity is mitigated by vitronectin in traumatic brain injury mouse model |
| title_short | Reactive astrocyte-derived neurotoxicity is mitigated by vitronectin in traumatic brain injury mouse model |
| title_sort | reactive astrocyte derived neurotoxicity is mitigated by vitronectin in traumatic brain injury mouse model |
| topic | Vitronectin Traumatic brain injury Astrocyte Neuronal cell death C3 |
| url | http://www.sciencedirect.com/science/article/pii/S2667242125001083 |
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