Treatment with gelsolin reduces brain inflammation and apoptotic signaling in mice following thermal injury.
Treatment with gelsolin reduces brain inflammation and apoptotic signaling in mice following thermal injury.
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DOI：
10.1186/1742-2094-8-118
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发表时间：
2011-09-21
影响因子：
9.3
通讯作者：
Yao YM
中科院分区：
文献类型：
--
作者：
Zhang QH;Chen Q;Kang JR;Liu C;Dong N;Zhu XM;Sheng ZY;Yao YM
烧伤幸存者会发展为长期认知障碍，并伴有脑部炎症和细胞凋亡的增加。Gelsolin是一种具有封顶和切断活性的肌动蛋白结合蛋白，在脓毒性反应中起着至关重要的作用。我们观察凝胶输注是否能减轻烧伤小鼠的神经损伤。烧伤15%体表面积的小鼠静脉注射牛血清白蛋白作为安慰剂（2 mg/kg），或低剂量（2 mg/kg）或高剂量（20 mg/kg）明胶。分别于烧伤后8、24、48和72小时采集样品。分析脾T细胞的免疫功能。采用苏木精/伊红染色检测脑病理，免疫组化检测活化胶质细胞和浸润性白细胞。实时荧光定量PCR检测脑细胞因子mrna， caspase-3检测细胞凋亡。采用神经元特异性烯醇化酶（NSE）和可溶性蛋白-100 （S-100）的酶联免疫吸附法测定神经损伤。最后用western blot检测脑磷酸化erk的表达。Gelsolin以剂量依赖的方式显著改善小鼠严重烧伤后的预后。与安慰剂组相比，高剂量凝胶林治疗提高了生存率（56.67%比30%）。虽然接受低剂量明胶（30%）治疗的小鼠的预后没有显著改善，但与安慰剂对照组相比，生存时间延长（43.1±4.5 h vs 35.5±5.0 h; P < 0.05）。大剂量凝胶可明显减轻烧伤引起的T细胞抑制。同时，脑内NSE和S-100含量降低，细胞因子mRNA表达降低，小胶质细胞活化受到抑制，CD11b+和CD45+细胞向脑内浸润增强，脑内异常得到显著改善。此外，高剂量凝胶治疗显著降低了烧伤后升高的caspase-3活性，同时下调了磷酸化erk的表达。外源性凝胶输注通过部分减轻脑内炎症和细胞凋亡，以及增强外周T淋巴细胞功能，提高烧伤小鼠的存活率。这些数据提示了一种新的有效的策略来对抗过度的神经炎症，并在严重烧伤的情况下保持认知。
Burn survivors develop long-term cognitive impairment with increased inflammation and apoptosis in the brain. Gelsolin, an actin-binding protein with capping and severing activities, plays a crucial role in the septic response. We investigated if gelsolin infusion could attenuate neural damage in burned mice. Mice with 15% total body surface area burns were injected intravenously with bovine serum albumin as placebo (2 mg/kg), or with low (2 mg/kg) or high doses (20 mg/kg) of gelsolin. Samples were harvested at 8, 24, 48 and 72 hours postburn. The immune function of splenic T cells was analyzed. Cerebral pathology was examined by hematoxylin/eosin staining, while activated glial cells and infiltrating leukocytes were detected by immunohistochemistry. Cerebral cytokine mRNAs were further assessed by quantitative real-time PCR, while apoptosis was evaluated by caspase-3. Neural damage was determined using enzyme-linked immunosorbent assay of neuron-specific enolase (NSE) and soluble protein-100 (S-100). Finally, cerebral phospho-ERK expression was measured by western blot. Gelsolin significantly improved the outcomes of mice following major burns in a dose-dependent manner. The survival rate was improved by high dose gelsolin treatment compared with the placebo group (56.67% vs. 30%). Although there was no significant improvement in outcome in mice receiving low dose gelsolin (30%), survival time was prolonged against the placebo control (43.1 ± 4.5 h vs. 35.5 ± 5.0 h; P < 0.05). Burn-induced T cell suppression was greatly alleviated by high dose gelsolin treatment. Concurrently, cerebral abnormalities were greatly ameliorated as shown by reduced NSE and S-100 content of brain, decreased cytokine mRNA expressions, suppressed microglial activation, and enhanced infiltration of CD11b+ and CD45+ cells into the brain. Furthermore, the elevated caspase-3 activity seen following burn injury was remarkably reduced by high dose gelsolin treatment along with down-regulation of phospho-ERK expression. Exogenous gelsolin infusion improves survival of mice following major burn injury by partially attenuating inflammation and apoptosis in brain, and by enhancing peripheral T lymphocyte function as well. These data suggest a novel and effective strategy to combat excessive neuroinflammation and to preserve cognition in the setting of major burns.
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影响因子：
9.3
作者：
Gatson JW;Maass DL;Simpkins JW;Idris AH;Minei JP;Wigginton JG
通讯作者：
Wigginton JG
DOI：
10.1073/pnas.96.22.12866
发表时间：
1999-10-26
影响因子：
11.1
作者：
Alessandrini, A;Namura, S;Bonventre, JV
通讯作者：
Bonventre, JV
影响因子：
3.3
作者：
Carlson, Deborah L.;Maass, David L.;Horton, Jureta W.
通讯作者：
Horton, Jureta W.
影响因子：
9.3
作者：
Barbizan R;Oliveira AL
通讯作者：
Oliveira AL
影响因子：
4
作者：
Hara, Hideo;Kataoka, Seiko;Tabira, Takeshi
通讯作者：
Tabira, Takeshi