Salidroside Inhibits Reactive Astrogliosis and Glial Scar Formation in Late Cerebral Ischemia via the Akt/GSK-3β Pathway

Preclinical Evidence and Possible Mechanisms of Rhodiola rosea L. and Its Components for Ischemic Stroke: A Systematic Review and Meta-Analysis

“…After going through the remaining full-text articles, 120 articles were excluded for at least one of following reasons: 1) the article was not a research about ischemic stroke; 2) not an in vivo study; 3) the intervention was a combination of RRC with potential effect on ischemic stroke; 4) the study did not access the effects of RRC on the animal model of ischemic stroke; 5) no control group. Finally, 15 eligible studies (Chen et al, 2009; Shi et al, 2012;Chen et al, 2014;Yu et al, 2014;Han et al, 2015;Atochin et al, 2016;Chen et al, 2016;Liu et al, 2018;Zhang et al, 2018;Zuo et al, 2018;Zhong et al, 2019;Li et al, 2020;Zhang et al, 2020;Dong et al, 2021) involving 345 animals were identified (Figure 1).…”

“…Three studies used C57BL/6 mice (n 67). The weight of rats ranged from 190 to 320 g, and the weight of mice ranged from 18 to 23 g. Cerebral ischemic injury in the included studies was induced by temporary middle cerebral artery occlusion (MCAO) in which ischemic time varied from 8 to 180 min (Chen et al, 2009;Shi et al, 2012;Chen et al, 2014;Yu et al, 2014;Han et al, 2015;Atochin et al, 2016;Liu et al, 2018;Zhang et al, 2018;Zuo et al, 2018;Zhong et al, 2019;Li et al, 2020;Zhang et al, 2020;Dong et al, 2021), and permanent MCAO (Chen et al, 2016). For anesthesia chosen in experiments, four studies (Shi et al, 2012;Han et al, 2015;Atochin et al, 2016;Zhang et al, 2020) used chloral hydrate, three studies (Zuo et al, 2018;Zhong et al, 2019) used isoflurane, four studies (Chen et al, 2016;Zhang et al, 2018;Li et al, 2020;Dong et al, 2021) used sodium pentobarbital, and the remaining four studies (Chen et al, 2009;Chen et al, 2014;Yu et al, 2014;Liu et al, 2018) did not report it.…”

“…The weight of rats ranged from 190 to 320 g, and the weight of mice ranged from 18 to 23 g. Cerebral ischemic injury in the included studies was induced by temporary middle cerebral artery occlusion (MCAO) in which ischemic time varied from 8 to 180 min (Chen et al, 2009;Shi et al, 2012;Chen et al, 2014;Yu et al, 2014;Han et al, 2015;Atochin et al, 2016;Liu et al, 2018;Zhang et al, 2018;Zuo et al, 2018;Zhong et al, 2019;Li et al, 2020;Zhang et al, 2020;Dong et al, 2021), and permanent MCAO (Chen et al, 2016). For anesthesia chosen in experiments, four studies (Shi et al, 2012;Han et al, 2015;Atochin et al, 2016;Zhang et al, 2020) used chloral hydrate, three studies (Zuo et al, 2018;Zhong et al, 2019) used isoflurane, four studies (Chen et al, 2016;Zhang et al, 2018;Li et al, 2020;Dong et al, 2021) used sodium pentobarbital, and the remaining four studies (Chen et al, 2009;Chen et al, 2014;Yu et al, 2014;Liu et al, 2018) did not report it. Ten studies utilized a dose gradient of RRC: one study (Atochin et al, 2016) used 5, 10 and 20 mg kg −1 intravenously, one study (Chen et al, 2016) used 20, and 40 mg kg −1 orally, one study (Han et al, 2015) used 15, and 30 mg kg −1 intraperitoneally, one study (Liu et al, 2018) used 2.5, 5, 10 and 20 mg kg −1 intravenously, two studies (Zhang et al, 2018;Li et al, 2020) used 25, 50 and 100 mg kg −1 intraperitoneally, one study used 20, 50 and 100 mg kg −1 intraperitoneally, one study …”

“…Ten studies utilized a dose gradient of RRC: one study (Atochin et al, 2016) used 5, 10 and 20 mg kg −1 intravenously, one study (Chen et al, 2016) used 20, and 40 mg kg −1 orally, one study (Han et al, 2015) used 15, and 30 mg kg −1 intraperitoneally, one study (Liu et al, 2018) used 2.5, 5, 10 and 20 mg kg −1 intravenously, two studies (Zhang et al, 2018;Li et al, 2020) used 25, 50 and 100 mg kg −1 intraperitoneally, one study used 20, 50 and 100 mg kg −1 intraperitoneally, one study (Zhong et al, 2019) used 20, 40, and 80 mg kg −1 intraperitoneally, one study (Zuo et al, 2018) used 10, 20, and 40 mg kg −1 intraperitoneally, and one study (Zhang et al, 2020) used 12 and 48 mg kg −1 through gavage. Six studies (Shi et al, 2012;Chen et al, 2014;Atochin et al, 2016;Chen et al, 2016;Zuo et al, 2018;Zhong et al, 2019) administrated RRC before stroke; Seven studies (Shi et al, 2012;Yu et al, 2014;Chen et al, 2016;Liu et al, 2018;Zhang et al, 2018;Zhang et al, 2020;Dong et al, 2021) administrated RRC after stroke; and two studies (Han et al, 2015;Li et al, 2020) administrated RRC before and after stroke. In the control group, twelve studies applied same volume of normal saline, one study (Liu et al, 2018) applied phosphate-buffered saline (PBS), one study (Zhang et al, 2020) applied distilled water and the remaining one study (Chen et al, 2015) did not clearly mentioned.…”

“…Nine studies (Shi et al, 2012;Yu et al, 2014;Han et al, 2015;Chen et al, 2016;Liu et al, 2018;Zhang et al, 2018;Zuo et al, 2018;Li et al, 2020) adopted IV as outcome measurements; fourteen studies (Chen et al, 2009;Shi et al, 2012;Chen et al, 2014;Yu et al, 2014;Han et al, 2015;Atochin et al, 2016;Liu et al, 2018;Zhang et al, 2018;Zuo et al, 2018;Zhong et al, 2019;Li et al, 2020;Zhang et al, 2020;Dong et al, 2021) used NFS as outcome measurements, among them eight studies (Shi et al, 2012;Yu et al, 2014;Han et al, 2015;Liu et al, 2018;Zhang et al, 2018;Zuo et al, 2018;Li et al, 2020) adopted both above two outcome measurements. However, the methods used to identify IV were different; eight studies (Shi et al, 2012;Yu et al, 2014;Han et al, 2015;Chen et al, 2016;Liu et al, 2018;Zhang et al, 2018;Zuo et al, 2018;Li et al, 2020) used TTC staining and one study used MRI scan.…”