Journal of Molecular Neuroscience

, Volume 66, Issue 2, pp 261–272 | Cite as

Neuregulin-1β Plays a Neuroprotective Role by Inhibiting the Cdk5 Signaling Pathway after Cerebral Ischemia-Reperfusion Injury in Rats

  • Rui Zhang
  • Cui Liu
  • Yaqing Ji
  • Lei Teng
  • Yunliang GuoEmail author


This study investigated the effects of neuregulin-1β (NRG1β) after middle cerebral artery occlusion/reperfusion (MCAO/R) in rats to evaluate whether they occur via the cyclin-dependent kinase (Cdk)5 signaling pathway. One hundred adult male Wistar rats were randomly divided into sham, MCAO/R, treatment (NRG1β), inhibitor (roscovitine; Ros), and inhibitor + treatment (Ros + NRG1β) groups. The MCAO/R model was established using the intraluminal thread method. The neurobehavioral function was evaluated by the modified neurological severity score (mNSS). The cerebral infarction volume (CIV) was measured by triphenyl tetrazolium chloride (TTC) staining. Morphological changes were observed by hematoxylin-eosin (HE) staining. The apoptotic cell index (ACI) was detected by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Immunohistochemistry and Western blotting were performed to detect the expression of calpain 1, p35/p25 (regulatory binding partners of Cdk5), Cdk5, and p-Tau in neurons. The neuronal morphology in the MCAO/R, NRG1β, Ros + NRG1β, and Ros groups differed compared to the sham group; the mNSS, CIV, ACI, and the expression of calpain 1, p35/p25, Cdk5, and p-Tau were significantly increased in all four groups (P < 0.05). In the NRG1β, Ros and Ros + NRG1β groups, the neuronal morphology was significantly improved compared to the MCAO/R group, as were the mNSS, CIV, and ACI. The levels of calpain 1, p35/p25, and p-Tau were decreased compared with the MCAO/R group (P < 0.05), while the Cdk5 expression was not significantly different (P > 0.05). NRG1β may exert neuroprotective effects by inhibiting the expression of calpain 1, p35/p25, and p-Tau after cerebral ischemia-reperfusion injury.


Cerebral ischemia Reperfusion injury Cdk5 Neuregulin-1β Signaling pathway 


Funding Information

This work was supported by grants from the National Natural Science Foundation of China (81274116), the Taishan Scholars Construction Project Excellent Innovative Team of Shandong Province, and the Youth Fund Project of the Affiliated Hospital of Qingdao University. None of these organizations was involved in the design, performance, collection of data, analysis, interpretation, or presentation of this study.

Compliance with Ethical Standards

The National Institutes of Health Guide for the Care and Use of Laboratory Animals was used as a guide for the design of all animal-related studies. All animal-related experiments were performed using protocols approved by our institute (The Ethics Committee of Qingdao University Medical College, QUMC 2011-09).

Conflicts of Interest

The authors declare that they have no conflicts of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of ICUAffiliated Hospital of Qingdao UniversityQingdaoChina
  2. 2.Department Traumic SurgeryAffiliated Hospital of Qingdao UniversityQingdaoChina
  3. 3.Institute of Integrative MedicineAffiliated Hospital of Qingdao UniversityQingdaoChina
  4. 4.Department of BiologyAffiliated Hospital of Qingdao UniversityQingdaoChina
  5. 5.Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao UniversityShandong Provincial Collaborative Innovation Center for Neurodegenerative DisordersQingdaoChina

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