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The Effect of PSD-93 Deficiency on the Expression of Early Inflammatory Cytokines Induced by Ischemic Brain Injury

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Abstract

The aim of the study was to explore the effect of PSD-93 deficiency on the expression of early inflammatory cytokines induced by cerebral ischemia/reperfusion injury. Ten- to twelve-week-old male PSD-93 knockout (PSD-93 KO) mice (C57BL/6 genetic background) and wild-type (WT) littermates were randomly divided into sham and ischemia/reperfusion (I/R) group. The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO) suture method. RT-PCR was used to detect the mRNA expression of IL-6, IL-10, Cox-2, iNOS, and TNF-α4h following reperfusion. Infarct volume at different time points after I/R was analyzed using 2,3,5-triphenyl tetrazolium staining, and neurological damage score (neurological severity scores, NSS) was used to evaluate the effect of PSD-93 gene knockout on the MCAO-induced neurological injury. In WT mice, early I/R injury led to the increase in the mRNA expression of proinflammatory cytokines IL-6, Cox-2, iNOS, and TNF-α that coincided with the decrease in the expression of anti-inflammatory cytokine IL-10, as compared to the sham group (P < 0.05). This effect was markedly attenuated by depleting PSD-93 levels by gene knockout. As compared to sham group, in PSD-93 KO mice I/R4h led to downregulation of Cox-2 and iNOS expression, and increase in the mRNA levels of IL-10 (P < 0.05). In addition, following MCAO, PSD-93 KO mice exhibited improved NSS and reduced infarct volumes, as compared with WT animals. PSD-93 knockout may play a neuroprotective role by mediating the early release of inflammatory cytokines induced by cerebral ischemia.

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Acknowledgments

We would like to thank Dr. Yuanxiang Tao for providing PSD-93 KO mice. This study was supported by the National Natural Science Foundation of China (81301120, 81200897), the Natural Science Foundation of the Colleges and Universities in Jiangsu Province (13KJB320027) and Xuzhou Medical Young Talents Project.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, Drum Tower Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China

    Qingxiu Zhang, Hongyu Cheng, Rong Rong & Yun Xu

  2. Department of Neurology, The Second Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221006, Jiangsu, China

    Qingxiu Zhang & Liangqun Rong

  3. Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, 210029, Jiangsu, China

    Qingxiu Zhang & Gang Hu

  4. Department of Neurosurgery, Xuzhou First People’s Hospital, Xuzhou, 221002, Jiangsu, China

    Hui Yang

  5. Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

    Qiuhong Ji

  6. Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221000, Jiangsu, China

    Qingjie Li

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  1. Qingxiu Zhang
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  2. Hongyu Cheng
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  3. Rong Rong
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  4. Hui Yang
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  5. Qiuhong Ji
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  6. Qingjie Li
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  7. Liangqun Rong
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  8. Gang Hu
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  9. Yun Xu
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Correspondence to Gang Hu or Yun Xu.

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Zhang, Q., Cheng, H., Rong, R. et al. The Effect of PSD-93 Deficiency on the Expression of Early Inflammatory Cytokines Induced by Ischemic Brain Injury. Cell Biochem Biophys 73, 695–700 (2015). https://doi.org/10.1007/s12013-015-0666-9

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