Citation

Chen W, Guo Y, Yang W, Chen L, Ren D, Wu C, He B, Zheng P, Tong W. J. Neurophysiol. 2018; 119(1): 305-311.

Affiliation

The People's Hospital of Pudong New Area wstong3@sina.com.

Copyright

(Copyright © 2018, American Physiological Society)

DOI

10.1152/jn.00654.2017

PMID

29046426

Abstract

Traumatic brain injury (TBI) caused by the external force leads to the neuronal dysfunction and even death. TBI has been reported to significantly increase the phosphorylation of glial gap junction protein connexin 43 (Cx43), which in turn propagates damages into surrounding brain tissues. However, the neuroprotective and anti-apoptosis effects of glia-derived exosomes have also been implicated in recent studies. Therefore, we detected whether TBI-induced phosphorylation of Cx43 would promote exosome release in rat brain. To generate TBI model, adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury. Phosphorylated Cx43 protein levels and exosome activities were quantified using western blot analysis following TBI. Long-term potentiation (LTP) was also tested in rat hippocampal slices. TBI significantly increased the phosphorylated Cx43 and exosome markers expression in rat ipsilateral hippocampus, but not cortex. Blocking the activity of Cx43 or ERK, but not JNK, significantly suppressed TBI-induced exosome release in hippocampus. Furthermore, TBI significantly inhibited the induction of LTP in hippocampal slices, which could be partially but significantly restored by pretreatment with exosomes. The results implicated that TBI-activated Cx43 could mediate a nociceptive effect by propagating the brain damages, as well as a neuroprotective effect by promoting exosome release.

Copyright © 2017, Journal of Neurophysiology.

Language: en

Keywords

ERK; connexin 43; exosome-based therapy; hippocampus; traumatic brain injury