Limb remote ischemic conditioning promotes myelination by upregulating PTEN/Akt/mTOR signaling activities after chronic cerebral hypoperfusion

Xiaohua Li, Changhong Ren, Sijie Li, Rongrong Han, Jinhuan Gao, Qingjian Huang, Kunlin Jin, Yinghao Luo, Xunming Ji

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)392-401
Number of pages10
JournalAging and Disease
Volume8
Issue number4
DOIs
StatePublished - 1 Jan 2017

Fingerprint

Extremities
Oligodendroglia
Myelin Sheath
Apoptosis
Corpus Callosum
Neuroprotective Agents
Phosphatidylinositol 3-Kinases
Carotid Arteries
Cognition
Conditioning (Psychology)
Signal Transduction
Ischemia
Western Blotting
Wounds and Injuries
Growth
White Matter

Keywords

  • Cerebral hypoperfusion
  • Ischemic conditioning
  • Oligodendrocyte
  • PI3K/Akt/mTOR
  • Vascular dementia
  • White matter

Cite this

Li, Xiaohua ; Ren, Changhong ; Li, Sijie ; Han, Rongrong ; Gao, Jinhuan ; Huang, Qingjian ; Jin, Kunlin ; Luo, Yinghao ; Ji, Xunming. / Limb remote ischemic conditioning promotes myelination by upregulating PTEN/Akt/mTOR signaling activities after chronic cerebral hypoperfusion. In: Aging and Disease. 2017 ; Vol. 8, No. 4. pp. 392-401.
@article{d9b517e314bb4a00882b37542989e28e,
title = "Limb remote ischemic conditioning promotes myelination by upregulating PTEN/Akt/mTOR signaling activities after chronic cerebral hypoperfusion",
abstract = "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.",
keywords = "Cerebral hypoperfusion, Ischemic conditioning, Oligodendrocyte, PI3K/Akt/mTOR, Vascular dementia, White matter",
author = "Xiaohua Li and Changhong Ren and Sijie Li and Rongrong Han and Jinhuan Gao and Qingjian Huang and Kunlin Jin and Yinghao Luo and Xunming Ji",
year = "2017",
month = "1",
day = "1",
doi = "10.14336/AD.2016.1227",
language = "English",
volume = "8",
pages = "392--401",
journal = "Aging and Disease",
issn = "2152-5250",
publisher = "International Society on Aging and Disease",
number = "4",

}

Limb remote ischemic conditioning promotes myelination by upregulating PTEN/Akt/mTOR signaling activities after chronic cerebral hypoperfusion. / Li, Xiaohua; Ren, Changhong; Li, Sijie; Han, Rongrong; Gao, Jinhuan; Huang, Qingjian; Jin, Kunlin; Luo, Yinghao; Ji, Xunming.

In: Aging and Disease, Vol. 8, No. 4, 01.01.2017, p. 392-401.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Limb remote ischemic conditioning promotes myelination by upregulating PTEN/Akt/mTOR signaling activities after chronic cerebral hypoperfusion

AU - Li, Xiaohua

AU - Ren, Changhong

AU - Li, Sijie

AU - Han, Rongrong

AU - Gao, Jinhuan

AU - Huang, Qingjian

AU - Jin, Kunlin

AU - Luo, Yinghao

AU - Ji, Xunming

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Cerebral hypoperfusion

KW - Ischemic conditioning

KW - Oligodendrocyte

KW - PI3K/Akt/mTOR

KW - Vascular dementia

KW - White matter

UR - http://www.scopus.com/inward/record.url?scp=85032263933&partnerID=8YFLogxK

U2 - 10.14336/AD.2016.1227

DO - 10.14336/AD.2016.1227

M3 - Article

AN - SCOPUS:85032263933

VL - 8

SP - 392

EP - 401

JO - Aging and Disease

JF - Aging and Disease

SN - 2152-5250

IS - 4

ER -