Experimental Brain Research

, Volume 237, Issue 12, pp 3351–3362 | Cite as

NRG1–ErbB4 signaling promotes functional recovery in a murine model of traumatic brain injury via regulation of GABA release

  • Weike Deng
  • Fei LuoEmail author
  • Bao-ming Li
  • Lin Mei
Research Article


Traumatic brain injury (TBI) is a serious health problem in the world. However, little is known about the pathogenesis and molecular mechanisms of TBI. Here, we show that TBI activates neuregulin 1 (NRG1)-ErbB4 signaling, with an increased expression of NRG1 and ErbB4 in the traumatic region. Specifically knocking out ErbB4 in parvalbumin-positive (PV+) interneurons exacerbates motor function deficits in mice after TBI. Consistently, PV-ErbB4−/− mice showed larger necrotic area and more edema when compared with PV-ErbB4+/+ mice. Replenishment of NRG1 through intranasal application of the recombinant protein in PV-ErbB4+/+ mice enhanced neurological function. Moreover, using an in vitro neuronal culture system, we found that NRG1–ErbB4 signaling protects neurons from glutamate-induced death, and such protective effects could be diminished by GABA receptor antagonist. These results indicate that NRG-ErbB4 signaling protects cortical neurons from TBI-induced damage, and such effect is probably mediated by promoting GABA activity. Taken together, these findings unveil a previously unappreciated role for NRG1-ErB4 signaling in preventing neuronal cell death during functional recovery after TBI.


NRG1–ErbB4 signaling Traumatic brain injury Neuroprotection GABA 



This research was supported by the National Natural Science Foundation of China (31971035, 81471116, 31771182, 81560196), and the Natural Science Foundation of Jiangxi Province (20171ACB20002).

Compliance with ethical standards

Conflict of interest

The authors declare no financial conflict of interest regarding the publication of this article.

Supplementary material

221_2019_5680_MOESM1_ESM.docx (646 kb)
Supplementary material 1 (DOCX 645 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Life ScienceNanchang UniversityNanchangPeople’s Republic of China
  2. 2.Institute of Life ScienceNanchang UniversityNanchangPeople’s Republic of China
  3. 3.Department of Neuroscience and Regenerative Medicine, Medical College of GeorgiaAugusta UniversityAugustaUSA
  4. 4.Charlie Norwood VA Medical CenterAugustaUSA

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