TABLE 1.
Neuroprotection of melatonin treatment in SAH.
| Therapeutic paradigm | Main findings | References |
| 5 mg or 10 mg/kg, injected into the cisterna magna at 1 h before SAH. | Melatonin prevents focal cerebellum injury by induction of HO-1. The antioxidant capability of melatonin is higher than vitamin E. | Martinez-Cruz et al., 2002 |
| 5 mg/kg, intraperitoneally injection every 12 h for 48 h, start at 2 h after SAH. | Melatonin prevents SAH-induced vasospasm and apoptosis of endothelial cells of vessels. | Aydin et al., 2005 |
| 15 mg or 150 mg/kg, intraperitoneally injection at 2 h after SAH. | High doses of melatonin (150 mg/kg) reduce brain edema and mortality after SAH. | Ayer et al., 2008b |
| 15 mg or 150 mg/kg, intraperitoneally injection at 2 h after SAH. | High doses of melatonin (150 mg/kg) reduce brain edema and mortality after SAH, which is unrelated to oxidative stress inhibition. | Ayer et al., 2008a |
| 10 mg/kg, intraperitoneally injection immediately after SAH, then daily for 2 days. | Melatonin alleviates oxidative stress, restores BBB permeability and reduces brain edema after SAH. | Ersahin et al., 2009 |
| 20 mg/kg, intraperitoneally injection at 6 h after SAH, twice daily for 5 days. | Melatonin alleviates cerebral vasospasm by elevating NO levels in serum and downregulating the levels of arginase and oxidative stress in the brain. | Aladag et al., 2009 |
| 5 mg/kg, intraperitoneally injection every 12 h for 120 h, start immediately after SAH. | Melatonin attenuates inflammatory response and oxidative stress in the spasmodic artery and alleviates cerebral vasospasm post-SAH. | Fang et al., 2009 |
| 150 mg/kg, intraperitoneally injection at 2 h and 24 h after SAH | Melatonin attenuates EBI via activating the Nrf2-ARE pathway and regulating oxidative stress by inducing antioxidant and detoxifying enzymes. | Wang et al., 2012 |
| 150 mg/kg, intraperitoneally injection at 2 and 24 h after SAH | Melatonin exerts neuroprotection through anti-oxidative and anti-inflammatory signaling pathways following SAH. | Wang et al., 2013 |
| 150 mg/kg, intraperitoneally injection at 2 h after SAH. | Melatonin improves the neurological outcome by reducing neuronal apoptosis and enhancing autophagy via a mitochondrial pathway. | Chen et al., 2014b |
| 150 mg/kg, intraperitoneally injection at 2 h after SAH. | Melatonin inhibits the degradation of tight junction proteins, attenuates cerebral edema, improves BBB dysfunctions by inhibiting the inflammatory response. | Chen et al., 2014a |
| 150 mg/kg, intraperitoneally injection at 2 h after SAH. | Melatonin attenuates neurogenic pulmonary edema by preventing alveolar-capillary barrier dysfunctions via repressing the inflammatory response and reducing apoptosis after SAH. | Chen et al., 2015 |
| 150 mg/kg, intraperitoneally injection at 2 h after SAH. | Melatonin attenuates the EBI post-SAH by inhibiting NLRP3 inflammasome-associated apoptosis. | Dong et al., 2016 |
| 150 mg/kg, intraperitoneally injection at 2 and 12 h after SAH. | Melatonin attenuates EBI following SAH via the MR/Sirt1/NF-κB signaling pathway. | Zhao et al., 2017 |
| 150 mg/kg, intraperitoneally injection at 2 h after SAH. | Melatonin exerts a neuroprotective effect after SAHA by inhibiting mitophagy-associated NLRP3 inflammasome. | Cao et al., 2017 |
| 150 mg/kg, intraperitoneally injection at 2 and 12 h after SAH. | Melatonin attenuates EBI after SAH by regulating the H19-miR-675-P53 and H19-let-7a-NGF signaling pathways. | Yang et al., 2018b |
| 15 mg or 150 mg/kg, intraperitoneally injection at 2 h after SAH. | Melatonin attenuates SAH-induced EBI by diminishing neuronal apoptosis and autophagy, partially involving the ROS-MST1 pathway. | Shi et al., 2018 |
| 150 mg/kg, intraperitoneally injection at 2 and 12 h after SAH. | Melatonin attenuates EBI after SAH by regulating the protein expression of SIRT3. | Yang et al., 2018a |
| 150 mg/kg, intraperitoneally injection at 2 and 12 h after SAH. | Melatonin provides protection against EBI post-SAH by inducing mitophagy and increasing the expression of NRF2. | Sun et al., 2018 |
| Intraperitoneally injection at 2 h after SAH. | Melatonin treatment attenuates EBI following SAH via the JAK1/STAT3 signaling pathway. | Li et al., 2019 |
| 150 mg/kg, intraperitoneally injection at 2 and 12 h after SAH. | Melatonin ameliorates cerebral vasospasm by regulating the H19/miR-138/eNOS and H19/miR-675/HIF1α signaling pathways. | Hou et al., 2020 |
| 50 mg/kg, 150 mg/kg, or 300 mg/kg, intraperitoneally injection at 15 min after SAH. | Melatonin exerts a white matter-protective effect in SAH pathophysiology, possibly by attenuating apoptosis in oligodendrocytes. | Liu et al., 2020 |
| 150 mg/kg, intraperitoneally injection at 12 h after SAH. | Melatonin ameliorates delayed brain injury following SAH via H19/miR-675/HIF1A/TLR4 signaling pathway. | Xu et al., 2022 |