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.

A novel squaramide compound alleviates cognitive deficits through activation of Akt and Erk1/2 in a rat model of vascular dementia

“…The effect of bpV(pis) was tested for the first time in the vascular dementia rats induced by 2VO. Consistent with previous findings, animal spatial cognitive function and memory functions and morphological structure in hippocampus tissue were impaired in the VD model (Chen et al, 2018b;Hu et al, 2017;Li et al, 2017;Ma et al, 2018), whereas bpV(pis) treatment significantly alleviated cognitive impairment and the morphological changes induced by 2VO.…”

Matrine induces senescence of human glioblastoma cells through suppression of the IGF1/PI3K/AKT/p27 signaling pathway

“…We found a significant correlation between AKT, PTEN, and matrine treatment. PTEN plays a vital role as a cellular tumor suppressor and regulates PI3K/AKT signaling . As PI3K/AKT is an important pathway in the regulation of cellular senescence, we further tested whether PI3K/AKT contributed to senescence in response to matrine treatment.…”

“…PTEN plays a vital role as a cellular tumor suppressor and regulates PI3K/AKT signaling. 26,27 As PI3K/AKT is an important pathway in the regulation of cellular senescence, 28,29 we further tested whether PI3K/AKT contributed to senescence in response to matrine treatment. Matrine treatment led to decreased expression of PI3K and pAKT in GBM cells, and activation of the signaling pathway partially restored cell growth when matrine-treated cells were simultaneously exposed to SC79, an activator of pAKT.…”

Limb Ischemic Conditioning Improved Cognitive Deficits via eNOS-Dependent Augmentation of Angiogenesis after Chronic Cerebral Hypoperfusion in Rats

“…CCH model was induced using the double carotid artery or 2-vessel occlusion (2VO) model as described previously [ 25 , 26 ]. Briefly, rats were anesthetized with 4.0% enflurane and then maintained on 1.5-2.0% enoflurane in 70% N 2 O and 30% O 2 using a small-animal anesthesia system.…”