Research Article: Limb Remote Ischemic Conditioning Promotes Myelination by Upregulating PTEN/Akt/mTOR Signaling Activities after Chronic Cerebral Hypoperfusion

Date Published: July 21, 2017

Publisher: JKL International LLC

Author(s): Xiaohua Li, Changhong Ren, Sijie Li, Rongrong Han, Jinhuan Gao, Qingjian Huang, Kunlin Jin, Yinghao Luo, Xunming Ji.


Limb Remote ischemic conditioning (LRIC) has been proved to be a promising neuroprotective method in white matter lesions after ischemia; however, its mechanism underlying protection after chronic cerebral hypoperfusion remains largely unknown. Here, we investigated whether LRIC promoted myelin growth by activating PI3K/Akt/mTOR signal pathway in a rat chronic hypoperfusion model. Thirty adult male Sprague Dawley underwent permanent double carotid artery (2VO), and limb remote ischemic conditioning was applied for 3 days after the 2VO surgery. Cognitive function, oligodendrocyte counts, myelin density, apoptosis and proliferation activity, as well as PTEN/Akt/mTOR signaling activity were determined 4 weeks after treatment. We found that LRIC significantly inhibited oligodendrocytes apoptosis (p<0.05), promoted myelination (p<0.01) in the corpus callosum and improved spatial learning impairment (p<0.05) at 4 weeks after chronic cerebral hypoperfusion. Oligodendrocytes proliferation, along with demyelination, in corpus callosum were not obviously affected by LRIC (p>0.05). Western blot analysis indicated that LRIC upregulated PTEN/Akt/mTOR signaling activities in corpus callosum (p<0.05). Our results suggest that LRIC exerts neuroprotective effect on white matter injuries through activating PTEN/Akt/mTOR signaling pathway after chronic cerebral hypoperfusion.

Partial Text

In this study, we found that LRIC reduced oligodendrocytes apoptosis, alleviated demyelination in corpus callosum, and improved spatial learning performance after chronic cerebral hypoperfusion in rats. In addition, we also found that p-Akt and p-mTOR ser 2448 was obviously up-regulated after LRIC treatment. Our findings suggest that LRIC attenuated demyelination partially via activating PTEN/Akt/mTOR1 pathway.




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