Activation of STAT3 is involved in neuroprotection by electroacupuncture pretreatment via cannabinoid CB1 receptors in rats.

Heng Zhou, Zhi Zhang, Haidong Wei, Feng Wang, Fan Guo, Zijun Gao, Giovanni Marsicano, Qiang Wang, Lize Xiong
Brain Research. 2013-09-01; 1529: 154-164
DOI: 10.1016/j.brainres.2013.07.006

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1. Brain Res. 2013 Sep 5;1529:154-64. doi: 10.1016/j.brainres.2013.07.006. Epub 2013
Jul 20.

Activation of STAT3 is involved in neuroprotection by electroacupuncture
pretreatment via cannabinoid CB1 receptors in rats.

Zhou H(1), Zhang Z, Wei H, Wang F, Guo F, Gao Z, Marsicano G, Wang Q, Xiong L.

Author information:
(1)Department of Anesthesiology, Xijing Hospital, Forth Military Medical
University, Xi’an 710032, Shaanxi Province, China.

Pretreatment with electroacupuncture (EA) attenuates cerebral ischemic injury
through the endocannabinoid system, although the molecular mechanisms mediate
this neuroprotection are unknown. It is well-known that signal transducer and
activator of transcription 3 (STAT3) plays an essential role in cell survival and
proliferation. Therefore, we investigated whether STAT3 is involved in EA
pretreatment-induced neuroprotection via cannabinoid CB1 receptors (CB1R) after
transient focal cerebral ischemia in rats. Two hours after EA pretreatment, focal
cerebral ischemia was induced by middle cerebral artery occlusion (MACO) for 120
min. The expression of pSTAT3(Ser727), which is necessary for STAT3 activation,
was examined in the ipsilateral ischemic penumbra. Infarct volumes and
neurological scores were evaluated at 72 h after MACO in the presence or absence
of the STAT3 inhibitor peptide (PpYLKTK). Neuronal apoptosis and the Bax/Bcl-2
ratio were also evaluated 24h after reperfusion. Our results showed that EA
pretreatment significantly enhanced neuronal expression of pSTAT3(Ser727) in the
ischemic penumbra 6h after reperfusion. Moreover, EA pretreatment reduced infarct
volume, improved neurological outcome, inhibited neuronal apoptosis and decreased
the Bax/Bcl-2 ratio following reperfusion. The beneficial effects of EA were
attenuated by PpYLKTK administered 30 min before MACO, and PpYLKTK effectively
reversed the increase in pSTAT3(Ser727) expression. Furthermore, CB1R antagonist
or CB1R knockdown with siRNA blocked the elevation of pSTAT3(Ser727) expression
by EA pretreatment, whereas the two CB1R agonists increased STAT3 activation. In
conclusion, EA pretreatment enhances STAT3 activation via CB1R to protect against
cerebral ischemia, suggesting that STAT3 activation may be a novel target for
stroke intervention.

Copyright © 2013 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.brainres.2013.07.006
PMID: 23880371 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus