Treatment with gelsolin reduces brain inflammation and apoptotic signaling in mice following thermal injury

Journal of Neuroinflammation

Yong-Ming Yao²  Zhi-Yong Sheng⁴  Xiao-Mei Zhu⁴  Ning Dong⁴  Chen Liu¹  Jia-Rui Kang³  Qi Chen⁴  Qing-Hong Zhang⁴ 

[1] Undergraduate Medical School, 4th Military Medical University, Xi'an, Shaanxi, 710032, PR China;State key laboratory of kidney disease, the Chinese PLA General Hospital, Beijing 100853, PR China;Department of Pathology, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, PR China;Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, PR China

关键词: Apoptosis;    Caspase-3;    Neuroinflammation;    Septic encephalopathy;    Gelsolin;    Burns;   

Others  :  1220800
DOI  :  10.1186/1742-2094-8-118

 received in 2011-05-13, accepted in 2011-09-21,  发布年份 2011

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusion

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.

【 授权许可】

   
2011 Zhang et al; licensee BioMed Central Ltd.

【 图 表 】

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