Complement C3 Participates in the Function and Mechanism of Traumatic Brain Injury at Simulated High Altitude
Complement C3 Participates in the Function and Mechanism of Traumatic Brain Injury at Simulated High Altitude
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补体C3参与模拟高海拔脑外伤的功能和机制
DOI：
10.1016/j.brainres.2019.146423
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发表时间：
2020-01
期刊：
影响因子：
2.9
通讯作者：
Gang Zhu
中科院分区：
文献类型：
--
作者：
Linjie Wei;Jianbo Zhang;Bo Zhang;Junjun Geng;Qiang Tan;Ling Wang;Zhi Chen;Hua Feng;Gang Zhu
背景创伤性脑损伤导致严重的死亡和残疾，其中补体激活引起的继发性损伤起着重要作用。与低海拔地区相比，发生在高海拔地区的脑损伤往往与更严重的脑水肿和更差的神经功能恢复有关。然而，这种差异的潜在机制尚不清楚。为此，我们利用眼镜蛇毒素因子(CVF)在模拟高原地区消耗补体C3，以探讨不同海拔高度的转归差异是否与补体C3引起的继发性损伤有关。将大鼠随机分为假手术组(Sham + ，Sham)、高原 + 脑损伤模型组(HAT)、高原 + 脑损伤模型组(H-CVF)、低海拔 + 模型组(LOW- + TBI + )和低海拔模型组(HIGH-CVF)。采用Evans蓝荧光、Perls染色、TUNEL染色、免疫组织化学和Western blotting等技术检测脑挫伤和脑水肿体积、脑含水量、髓鞘碱性蛋白(MBP)表达、肿瘤坏死因子-α(TNF-α)表达、白介素1β(IL1B)表达、死亡率、神经功能和补体成分3(C3)mRNA表达，以评价补体激活与继发性损伤的相关性。与低海拔颅脑损伤相比，高海拔颅脑损伤导致血脑屏障渗漏，更严重的脑水肿和更高的死亡率。此外，与低海拔脑损伤相比，高原脑损伤往往与更多的MBP降解、铁沉积、神经元凋亡和炎性因子沉积有关。用CVF抑制补体活化可部分逆转脑损伤的上述作用。结论本研究提供了高原脑损伤可导致严重的水肿和高死亡率及致残率的证据。补体C3的激活是继发性脑损伤的重要因素之一。
BackgroundTraumatic brain injury (TBI) leads to severe mortality and disability, in which secondary injury induced by complement activation plays an important role. TBI tends to be associated with more severe cerebral edema and worse neurological functional recovery if it occurs in high-altitude areas than in low-altitude areas. However, the underlying mechanism of this difference is unknown. Thus, we used cobra venom factor (CVF) to deplete complement C3 in simulated high-altitude areas to explore whether the differences in outcome at different altitudes are related to secondary injury caused by complement C3.MethodsThe weight-drop model was adopted to induce TBI in rats. Rats were randomly divided into the following groups: sham + saline (sham), high altitude + TBI + saline (HAT), high altitude + TBI + CVF (H-CVF), low altitude + TBI + saline (LAT), and low altitude + TBI + CVF (L-CVF). Brain contusion and edema volumes, brain water content, myelin basic protein (MBP) expression, tumor necrosis factor alpha (TNF-a) expression, interleukin 1 beta (IL1B) expression, mortality rate, neurological function, and complement component 3 (C3) mRNA expression were measured by techniques such as Evans blue fluorescence, Perls staining, TUNEL staining, ELISA, immunohistochemistry and Western blotting to evaluate correlations between complement activation and secondary injury.ResultsThe activation of complement after TBI was significantly higher at high altitude than at low altitude. High-altitude TBI resulted in a leakier blood-brain barrier, more severe cerebral edema and higher mortality than low-altitude TBI did. In addition, high-altitude TBI tended to be associated with more MBP degradation, ferric iron deposition, neuronal apoptosis, and inflammatory factor deposition than low-altitude TBI. All of these effects of TBI were partially reversed by inhibiting complement activation using CVF.ConclusionOur study provided evidence that TBI at high altitude leads to severe edema and high mortality and disability rates. Complement C3 activation is one of the important factors contributing to secondary brain injury.
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影响因子：
2
作者：
R. Dmochowski
通讯作者：
R. Dmochowski
DOI：
10.1016/j.respe.2020.09.004
发表时间：
2020-10-10
期刊：
Revue D'Epidemiologie et De Sante Publique
影响因子：
--
作者：
La rédaction
通讯作者：
La rédaction
影响因子：
9.3
作者：
通讯作者：
--
影响因子：
5.9
作者：
Craighead FL
通讯作者：
Craighead FL