Abstract
Neuregulin1β (NRG1β), a member of the excitomotor of tyrosine kinase receptor (erbB) family, was recently shown to play a neuroprotective role in cerebral ischemia–reperfusion injury. The present study analyzed the effects and its possible signaling pathway of NRG1β on brain tissues after cerebral ischemia–reperfusion injury. A focal cerebral ischemic model was established by inserting a monofilament thread to achieve middle cerebral artery occlusion, followed by an NRG1β injection via the internal carotid artery. NRG1β injection resulted in significantly improved neurobehavioral activity according to the modified neurological severity score test. Tetrazolium chloridestaining revealed a smaller cerebral infarction volume; hematoxylin-eosin staining and transmission electron microscopy showed significantly alleviated neurodegeneration in the middle cerebral artery occlusion rats. Moreover, expression of phosphorylated MEK5, phosphorylated ERK5, and phosphorylated MEK2C increased after NRG1β treatment, and the neuroprotective effect of NRG1β was attenuated by an injection of the MEK5 inhibitor, BIX02189. Results from the present study demonstrate that NRG1β provides neuroprotection following cerebral ischemia–reperfusion injury via the ERK5-dependent MAPK pathway.
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Abbreviations
- erbB:
-
Excitomotor of tyrosine kinase receptor
- MCAO:
-
Middle cerebral artery occlusion
- mNSS:
-
Modified neurological severity score
- HE:
-
Hematoxylin-eosin
- TTC:
-
Tetrazolium chloride
- CIV:
-
Cerebral infarct volume
- TEM:
-
Transmission electron microscopy
- rCBF:
-
Regional cerebral blood flow
- LDF:
-
Laser Doppler flowmeter
- DCI:
-
denatured cell number
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Acknowledgements
We thank Dr. Yanhong Wu for critically revising the manuscript.
Funding
This publication was supported by Chinese National Natural Science Foundation 81274116 (belongs to Qingdao University Medical College) to YG.
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The authors declare that they have no conflicts of interest.
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Ning Gu and Keli Ge contributed equally to this work.
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Figure S1
rCBF of MCAO model rats. A. Normal rCBF prior to insertion of line plug. B. The rCBF after insertion of line plug. C. The rCBF after cerebral ischemia-reperfusion (GIF 65 kb)
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Gu, N., Ge, K., Hao, C. et al. Neuregulin1β Effects on Brain Tissue via ERK5-Dependent MAPK Pathway in a Rat Model of Cerebral Ischemia–Reperfusion Injury. J Mol Neurosci 61, 607–616 (2017). https://doi.org/10.1007/s12031-017-0902-4
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DOI: https://doi.org/10.1007/s12031-017-0902-4