Preventive Cold Acclimation Augments the Reparative Function of Endothelial Progenitor Cells in Mice

Abstract

Background/Aims: Chronic cold exposure may increase energy expenditure and contribute to counteracting obesity, an important risk factor for cerebrocardiovascular diseases. This study sought to evaluate whether preventive cold acclimation before ischemia onset might be a promising option for preventing cerebral ischemic injury. Methods: After a 14-day cold acclimation period, young and aged mice were subjected to permanent cerebral ischemia, and histological analyses and behavioral tests were performed. Mouse endothelial progenitor cells (EPCs) were isolated, their function and number were determined, and the effects of EPC transplantation on cerebral ischemic injury were investigated. Results: Preventive cold acclimation before ischemia onset increased EPC function, promoted ischemic brain angiogenesis, protected against cerebral ischemic injury, and improved long-term stroke outcomes in young mice. In addition, transplanted EPCs from cold-exposed mice had a greater ability to reduce cerebral ischemic injury and promote local angiogenesis compared to those from control mice, and EPCs from donor animals could integrate into the recipient ischemic murine brain. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury, which could be improved by preventive cold acclimation. Moreover, preventive cold acclimation could also enhance EPC function, promote local angiogenesis, and protect against cerebral ischemic injury in aged mice. Conclusions: Preventive cold acclimation before ischemia onset improved long-term stroke outcomes in mice at least in part via promoting the reparative function of EPC. Our findings imply that a variable indoor environment with frequent cold exposure might benefit individuals at high risk for stroke.

Sodium Dichloroacetate Stimulates Angiogenesis by Improving Endothelial Precursor Cell Function in an AKT/GSK-3β/Nrf2 Dependent Pathway in Vascular Dementia Rats

“…After cells were allowed to migrate for 24 h (37°C, 5% CO 2 ), the EPCs were stained with Hochest 33258 (Sigma, MO, United States) for 15 min and fixed in 2% paraformaldehyde. The number of adherent cells were randomly counted in three fields (magnification × 100) of each sample, and the average of each sample was determined (Xin et al, 2016; Peng et al, 2018).…”

“…Approximately 1 × 10 4 EPCs were uniformly plated in a 96-well plate that was pre-coated with rat vitronectin (1 μg/mL) and incubated at 37°C in 5% CO 2 for 2 h. PBS was used to wash away non-adherent cells, and EPCs were stained with Hoechst 33258 for 15 min. The number of adherent cells was randomly counted in three fields (magnification × 100) of each sample, and the average numbers of adherent cells in each sample was determined (Peng et al, 2018).…”

“…Intracellular ROS levels were determined using dihydroethyl ingot (DHE) (Beyotime, China) staining (Xin et al, 2016; Peng et al, 2018). After 7 days of culture, EPCs from each group were collected and incubated with DHE (10 −6 mol/ L) for 30 min in the dark.…”