The role of aquaporin 4 in apoptosis after intracerebral hemorrhage

Journal of Neuroinflammation

Qiang Dong³  Yuping Tang³  Hongyan Ding³  Jingjing Su¹  Pin Wu²  Jun Xiang⁴  Heling Chu³ 

[1] Department of Neurology, Shanghai Ninth People¿s Hospital Affiliated Shanghai Jiaotong University School of Medicine, No. 639 Zhizaoju Road, Shanghai 200011, P. R. China;Department of Neurology, the Second Hospital of Zhejiang University Medical College, No. 88 Jiefang Road, Hangzhou 310009, P. R. China;Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, No. 12 Mid. Wulumuqi Road, Shanghai 200040, P. R. China;Department of Chinese Integrative Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, P. R. China

关键词: intracerebral hemorrhage;    cytokine;    aquaporin-4;    apoptosis;   

Others  :  1150292
DOI  :  10.1186/s12974-014-0184-5

 received in 2014-06-20, accepted in 2014-10-12,  发布年份 2014

【 摘 要 】

Background

We previously reported that aquaporin-4 deletion (AQP4^?/?) in mice increased edema and altered blood-brain barrier integrity following intracerebral hemorrhage (ICH). To date, little is known about the role of AQP4 in apoptosis after ICH. The purpose of this study was to examine the role of AQP4 in apoptosis and its mechanisms after ICH using AQP4^?/? mice.

Methods

We compared the survival rate and neurological deficits in wild-type (AQP4^+/+) mice with those in AQP4^?/? mice following ICH. Histological changes were detected with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and Hoechst staining. The cell types involved were determined by immunocytochemical studies. We also measured activated caspase-3, caspase-9, caspase-8, Bax, and Bcl-2 with Western blotting at 1, 3, and 7 days after ICH. A cytokine protein assay was used to detect cytokines in AQP4^+/+ and AQP4^?/? mice following ICH, and the results were verified by ELISA.

Results

We found more apoptotic cells in AQP4^?/? mice following ICH; the cell types involved were predominantly neurons and astrocytes. Western blotting showed that the expression of activated caspase-3 and caspase-8 was significantly increased (P <0.05). Moreover, we demonstrated a greater enhancement in the release of TNF-? and IL-1?, as well as their receptors, in AQP4^?/? mice following ICH than in AQP4^+/+ mice by cytokine protein assay and Western blotting (P <0.05). The inhibitors of TNF-? and IL-1? reduced apoptotic cells after ICH in AQP4^?/? mice compared with wild-type mice (P <0.05).

Conclusions

AQP4 deletion increases apoptosis following ICH, and the underlying mechanism may be through cytokines, especially TNF-? and IL-1?, initiating the apoptotic cascade, as well as activation of caspase-3 and caspase-8.

【 授权许可】

   
2014 Chu et al.; licensee BioMed Centra Ltd.

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