Table 1.

The main findings of melatonin-mediated neuroprotection in hemorrhagic stroke

Model	Therapeutic paradigm	Main findings	References
Cisterna magna model of SAH, rat	10 mg/kg, i.p., repeated daily for 2 days after SAH	Inhibits lipid peroxidation, restores glutathione levels	Ersahin et al. (2009)
Prechiasmatic cistern model of SAH, rat	150 mg/kg, i.p., 2 and 24 h after SAH	Activates Nrf2-ARE pathway, increases the expression of antioxidant and detoxifying enzymes	Wang et al. (2012)
Endovascular filament model of SAH, rat	150 mg/kg, i.p., 2 and 24 h after SAH	Reduces brain water content, decreases mortality	Ayer et al. (2008)
Endovascular filament model of SAH, rat	150 mg/kg, i.p., 2 h after SAH	Enhances autophagy, inhibits mitochondrial- dependent apoptosis	Chen et al. (2014b)
Endovascular filament model of SAH, rat	150 mg/kg, i.p., 2 h after SAH	Inhibits cortical expressions of proinflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α), maintains tight junction proteins and BBB integrity	Chen et al. (2014a)
Prechiasmatic cistern model of SAH, rat	150 mg/kg, i.p., 2 and 24 h after SAH	Lessens the protein expressions of TLR4 pathway-related mediators	(Wang et al. 2013b)
Cisterna magna model of SAH, rabbit	5 mg/kg, i.p., every 12 h after SAH for 5 days	Reduces arterial NF-κB binding activity, decreases vascular levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α), enhances the antioxidant defense system, reduces lipid peroxidation	Fang et al. (2009)
Collagenase -induced ICH model, rat	15 mg/kg, oral, every 24 h after ICH for 7 days	Reduces oxidative stress, enhances electrical responsiveness	Ueda et al. (2014)
Collagenase -induced ICH model, rat	15 or 150 mg/kg, i.p., 15 min or 3 h after ICH	Decreases lipid peroxidation	Rojas et al. (2008)
Collagenase -induced ICH model, rat	15 mg/kg, i.p., 1, 24, 48, and 72 h after ICH	Do not improve short-term outcomes	Hartman et al. (2008)
Collagenase -induced ICH model, rat	5 mg/kg, i.p., 1 h and every 24 h after ICH for 3 days	Alleviates long-term brain atrophy and reverses striatal and cognitive functional deficits	Lekic et al. (2010)
60-min transient MCAO model, mice	5 mg/kg, i.p., 60 min after the initiation of ischemia	Attenuates the postischemic increase in BBB permeability and decreases HT of t-PA therapy following ischemic stroke	Chen et al. (2006b)
60-min transient MCAO model, mice	5 mg/kg, i.p., 60 min after the initiation of ischemia	Mitigates excessive production of ROS and RNS, improves BBB integrity, and decreases HT of t-PA therapy following ischemic stroke	Chen et al. (2006a)
90-min transient MCAO model, rat	5 mg/kg, i.v., 90 min after the initiation of ischemia	Negatively regulates postischemic expression and activation of MMP-9, decreases HT of t-PA therapy following ischemic stroke	Hung et al. (2008)
60-min transient MCAO model, mice	5 mg/kg, i.v., 60 min after the initiation of ischemia	Increases the expression of TIMP-1, enhances the activity of PAI-1, reduces the activity of u-PA, inhibits the enzyme activity and protein expression of MMP-9, and decreases HT of t-PA therapy following ischemic stroke	Tai et al. (2010)