Neurochemical Research

, Volume 41, Issue 12, pp 3407–3416 | Cite as

Increased Expression of Caspase-12 After Experimental Subarachnoid Hemorrhage

  • Hua Li
  • Jia-Sheng Yu
  • Hua-Sheng Zhang
  • Yi-Qing Yang
  • Li-Tian Huang
  • Ding-Ding Zhang
  • Chun-Hua HangEmail author
Original Paper


Convincing evidences have proved that apoptosis plays a vital role in the pathogenesis of early and delayed brain injury following subarachnoid hemorrhage (SAH). Recently, a novel caspase-12-mediated apoptotic pathway has been reported to be induced by excess endoplasmic reticulum (ER) stress. Extensive protein damage occurs after SAH, which may trigger ER stress-associated apoptotic pathway. Thus, we hypothesized that caspase-12, as the major molecular marker of this novel apoptotic pathway, may be activated and involved in the pathogenesis of apoptotic injury after SAH. This study sought to investigate the changes of caspase-12 expressions in both in vitro and in vivo SAH models. Western blot analysis found significantly increased protein expressions of both pro- and active forms of caspase-12 after SAH. Quantitative real-time PCR and immunohistochemistry assays confirmed elevated caspase-12 level after SAH in vivo. Further, double immunofluorescence staining revealed obvious caspase-12 over-expression in both cortical neurons and astrocytes. Moreover, immunofluorescent co-staining in vivo demonstrated that neural cells with high immunoreactivity of caspase-12 also expressed caspase-3, and dual-immunofluorescent staining for caspase-12 and TUNEL in vitro showed that TUNEL-positive cells were more likely to exhibit higher caspase-12 immunoreactivity, indicating a potential contribution of caspase-12 activation to apoptosis in SAH. Collectively, our results showed significant upregulation of caspase-12 expression after experimental SAH. These findings also offer important implications for further investigations of the therapeutic potential of caspase-12 associated apoptosis in SAH.


Apoptosis Caspase-12 Caspase-3 Endoplasmic reticulum stress Subarachnoid hemorrhage 









Endoplasmic reticulum




Glialfibrillary acidic protein


Neuron specific nuclear protein


Phosphate-buffered saline


Polymerase chain reaction


Subarachnoid hemorrhage


Terminal deoxynucleotidyl transferase dUTP nick-end labeling



This study was supported by grants from the National Natural Science Foundation of China (No. 81371294 and No. 81601008) and the Natural Science Foundation of Jiangsu Province (No. BK20141375).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that there is no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Hua Li
    • 1
  • Jia-Sheng Yu
    • 1
  • Hua-Sheng Zhang
    • 2
  • Yi-Qing Yang
    • 2
  • Li-Tian Huang
    • 3
  • Ding-Ding Zhang
    • 2
  • Chun-Hua Hang
    • 2
    Email author
  1. 1.Department of Neurosurgery, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Department of Neurosurgery, Jinling Hospital, School of MedicineNanjing UniversityNanjingChina
  3. 3.Department of NeurosurgeryFourth Affiliated Hospital of Guangxi Medical UniversityLiuzhouChina

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