TABLE 2.
Protective effects of melatonin on in vivo cerebral I/R injury model or ischemic stroke model.
| Route | Time | Dose (mg/kg) | Effect | Mechanism | References |
|---|---|---|---|---|---|
| Sprague-Dawley rats | |||||
| i.p. | 3 h before MCAO | 50 | reduced brain infarct volume, improved neurological function | anti-oxidative stress, anti-apoptosis, alleviated mitochondrial dysfunction | Yip et al. (2021) |
| i.p. | 30 min before MCAO | 5 | reduced brain infarct volume, improved neurological function | anti-oxidative stress, anti-inflammation, anti-apoptosis, inhibited glutamate excitotoxicity | Pei et al. (2002), Pei and Cheung, 2004; Koh (2008a), Koh, 2008b; Koh (2008c), Koh, 2008d; Koh (2008e), Koh (2011), Koh, 2012a; Koh, 2012b; Li et al., 2014; Shah et al., 2018; Shah et al., 2019; Ling et al., 2020 |
| i.p. | 30 min before MCAO | 10 | reduced brain infarct volume, improved neurological function | anti-inflammation, anti-apoptosis | Liu and Cheung, 2013; Ma et al., 2013; Xu and Cheung, 2023 |
| i.p. | 30 min before MCAO | 15 | reduced brain infarct volume | anti-oxidative stress | Pei et al. (2002), Pei et al. (2002) |
| i.p. | 30 min before MCAO | 50 | reduced brain infarct volume, preserved BBB integrity | anti-oxidative stress | Pei et al. (2002), Pei et al. (2003) |
| i.p. | 30 min after MCAO | 10, 20, 40 | improved neurological function | anti-apoptosis | Chen et al. (2022) |
| i.p. | 1 h after MCAO | 5 | reduced brain infarct volume | - | Pei et al., (2003) |
| i.p. | 5 min before reperfusion | 10 | reduced brain infarct volume and brain edema, improved neurological function | anti-oxidative stress, anti-apoptosis | Gupta et al. (2004) |
| i.p. | immediately before reperfusion | 10 | reduced brain infarct volume | anti-apoptosis | Sung et al. (2009) |
| i.p. | 30 min after reperfusion | 50 | reduced brain infarct volume, improved neurological function | anti-oxidative stress, anti-apoptosis, alleviated mitochondrial dysfunction | Chen et al. (2021) |
| i.p. | 1.5, 24, 48 h after reperfusion | 20,50 | educed brain infarct volume, improved neurological function | anti-oxidative stress, anti-inflammation | Lin et al. (2019) |
| i.p. | 6, 24, 48 h after reperfusion | 30 | reduced brain infarct volume, improved neurological function | anti-oxidative stress, anti-apoptosis, alleviated mitochondrial dysfunction | Chen et al. (2021) |
| i.p. | once daily before MCAO | 10 | reduced brain infarct volume and brain edema, improved neurological function | inhibited autophagy | Feng et al. (2017) |
| i.p. | once daily after MCAO | 5, 10 | reduced brain infarct volume, improved neurological function | anti-oxidative stress, anti-inflammation, anti-apoptosis, inhibited autophagy | Nair et al., 2011; Zheng et al., 2014; Hao et al., 2021 |
| i.p. | twice daily after PT | 50 | preserved BBB integrity | anti-inflammation | Jang et al. (2012) |
| i.p. | 30 min before MCAO and 30 min after reperfusion | 5 | reduced brain infarct volume and brain edema, improved neurological function | anti-oxidative stress, anti-inflammation | Zhao et al., 2018; Zhao et al., 2019a |
| i.p. | 15 min before MCAO and 6, 12 h after reperfusion | 10 | reduced brain infarct volume | anti-oxidative stress, anti-apoptosis | Sun et al. (2002) |
| i.v. | immediately before reperfusion | 5 | reduced brain infarct volume and brain edema, improved neurological function | anti-inflammation, anti-apoptosis, inhibited glutamate excitotoxicity | Lee et al., 2004; Lee et al., 2007; Hung et al., 2008; Chen et al., 2009; Juan et al., 2014; Lin et al., 2018 |
| i.v. | immediately before reperfusion | 15, 50 | reduced brain infarct volume, improved neurological function | anti-oxidative stress, anti-inflammation | Tai et al. (2011) |
| s.c. | 30 min before MCAO | 4 | - | anti-oxidative stress | Li et al. (1997) |
| s.c. | 15 min before and 6, 12 h after MCAO | 2.5, 5, 10 | reduced brain infarct volume | anti-apoptosis | Ling et al. (1999) |
| Wistar rats | |||||
| i.p. | 24 h before MCAO | 10 | reduced brain infarct volume | anti-inflammation, anti-apoptosis | Rancan et al. (2018) |
| i.p. | 1 h before PT | 100 | reduced brain infarct volume | anti-oxidative stress | Matejovska et al. (2008) |
| i.p. | 30 min before and immediately before MCAO | 10 | improved neurological function | anti-oxidative stress, anti-apoptosis | Ahmad et al. (2011) |
| i.p. | immediately before reperfusion | 10 | reduced brain infarct volume, improved neurological function | anti-inflammation, anti-apoptosis | Yawoot et al. (2023) |
| i.p. | 10 min after PT | 100 | improved neurological function | anti-oxidative stress | Deykun et al. (2011) |
| i.p. | 1h after reperfusion and once daily after MCAO | 10 | reduced brain infarct volume | anti-apoptosis | Yilmaz et al. (2023) |
| i.p. | 0, 1.5 h after MCAO and 0, 1 h after reperfusion | 20 | reduced brain infarct volume, improved neurological function | anti-oxidative stress | Gupta et al. (2002) |
| i.p. | 0, 1 h after MCAO and reperfusion | 10, 20, 40 | reduced brain infarct volume, improved neurological function | anti-oxidative stress | Sinha et al. (2001) |
| i.p. | once daily after MCAO | 10 | reduced brain infarct volume, improved neurological function | anti-oxidative stress, anti-inflammation, anti-apoptosis | Rancan et al. (2018) |
| i.p. | immediately before MCAO and reperfusion | 10 | reduced brain infarct volume | anti-apoptosis | Ma et al. (2013) |
| i.p. | immediately before and once daily after reperfusion | 3, 10 | reduced brain infarct volume, improved neurological function | anti-inflammation | Yawoot et al. (2022) |
| i.a. | at the end of reperfusion | 4 | reduced brain infarct volume, improved neurological function | anti-inflammation | Azedi et al. (2019) |
| p.o. | once daily after reperfusion | 10 | reduced brain infarct volume | anti-oxidative stress, anti-inflammation | Saleh et al. (2020) |
| p.o. | 24 h before and 24 h after MCAO | 10 | reduced brain infarct volume | anti-inflammation, anti-apoptosis | Paredes et al. (2015) |
| p.o. | 1 h before and 24 h after MCAO | 6 | reduced brain edema | anti-oxidative stress | Kondoh et al., 2002; Torii et al., 2004 |
| p.o. | 1 h before and once daily after MCAO | 0.87–0.1 | reduced brain infarct volume | - | Borlongan et al. (2000) |
| Charles Foster rats | |||||
| i.p. | 30 min before and 1, 2 h after MCAO | 1, 3, 5, 7, 9 | reduced brain infarct volume and brain edema, improved neurological function | - | Bhattacharya et al. (2014) |
| C57BL/6j mice | |||||
| i.p. | before MCAO | 10 | reduced brain infarct volume, brain edema | anti-oxidative stress, anti-apoptosis | Zang et al. (2020) |
| i.p. | 5 min after PT | 1 | reduced brain infarct volume | anti-oxidative stress, anti-apoptosis, inhibited glutamate excitotoxicity | Buendia et al. (2015) |
| i.p. | 0, 24, 48 h after MCAO | 5, 10, 20 | reduced brain infarct volume, improved neurological function | anti-apoptosis | Ran et al. (2021) |
| i.p. | immediately before reperfusion | 4 | reduced brain infarct volume and brain edema, preserved BBB integrity | anti-apoptosis | Kilic et al., 2004; Kilic et al. 2005a; Kilic et al. 2005b; Kilic et al. 2013; Kilic et al. 2017 |
| i.p. | immediately before reperfusion | 5 | reduced brain infarct volume, improved neurological function, preserved BBB integrity | anti-oxidative stress | Lee et al., 2005; Chen, Chen, et al., 2006; Chen et al., 2006 |
| i.p. | immediately before reperfusion | 15 | reduced brain infarct volume, improved neurological function, preserved BBB integrity | anti-oxidative stress, anti-inflammation | Parada et al., 2014; Chen, Sun, et al., 2022 |
| i.p. | once daily after MCAO | 4 | improved neurological function | anti-inflammation | Kilic et al. (2021) |
| i.p. | 1 h before and 30 min after MCAO | 10 | reduced brain infarct volume | anti-apoptosis | Wang et al. (2009) |
| i.p. | 30 min before and 24, 48 h after PT | 15 | reduced brain infarct volume | anti-inflammation | Zou et al. (2004) |
| i.p. | immediately before MCAO and reperfusion | 4 | reduced brain infarct volume | anti-apoptosis | Kilic et al. (2004) |
| i.p. | immediately before MCAO and reperfusion | 5, 10 | reduced brain infarct volume and brain edema, improved neurological function | anti-oxidative stress, anti-apoptosis, alleviated mitochondrial dysfunction | Yang et al., 2015; Liu et al., 2021 |
| i.p. | immediately before MCAO and reperfusion | 10 | reduced brain infarct volume, improved neurological function | anti-oxidative stress, anti-apoptosis | Liu et al. (2021) |
| i.p. | immediately before MCAO and reperfusion | 20 | reduced brain infarct volume, improved neurological function | anti-apoptosis | Liu et al. (2019) |
| i.p. | immediately before and once daily after MCAO | 20 | reduced brain infarct volume, improved neurological function | anti-inflammation | Li et al. (2023) |
| i.p. | 3 days before and once daily after MCAO | 20, 50 | reduced brain infarct volume | anti-oxidative stress, anti-inflammation | Chen et al. (2020) |
| i.v. | 1 h after MCAO | 5 | reduced brain infarct volume | anti-oxidative stress | Tai et al. (2010) |
| i.v. | 0, 24 h after reperfusion | 20 | reduced brain infarct volume, improved neurological function | anti-inflammation | Liu et al. (2019) |
| p.o. | once daily after MCAO | 4 | improved neurological function | - | Kilic et al. (2008) |
| Balb/c mice | |||||
| i.p. | 1 min after reperfusion | 4 | reduced brain infarct volume and brain edema, improved neurological function | anti-apoptosis | Beker et al. (2015) |
| ICR mice | |||||
| i.p. | once daily after MCAO | 5, 10 | reduced brain infarct volume, improved neurological function | anti-oxidative stress, anti-inflammation | Chern et al. (2012) |
| 129/C57BL mice | |||||
| i.p. | 30 min before and 24, 48 h after PT | 15 | reduced brain infarct volume | anti-inflammation | Zou et al. (2006) |
| B6CBA mice | |||||
| i.p. | 1 h after and once daily after MCAO | 15 | reduced brain infarct volume | anti-inflammation | Suofu et al. (2023) |
i.p.: intraperitoneal; i.v.: intravenous; p.o.: peros; s.c.: subcutaneous; i.a.: intra-arterial; MCAO/R: middle cerebral artery occlusion/reperfusion; PT: photothrombotic stroke; BBB: blood-brain barrier.