Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

Table 2

The development for antioxidative treatment of ICH.

Drug name	Administration	Probable mechanism of action or drug targeting	Preclinical or clinical	References
PQQ	Pretreated with 10 mg/kg	Exhibited increased ratio of Bcl-2/Bax, alleviative to activated caspase-3	Rat model of ICH	[129]
Melatonin	150 mg/kg/d, ip; 5 mg/kg/12 h, ip; 15 or 150 mg/kg, ip	Attenuated inflammatory response (IL-1β, IL-6, and TNF-α, NF-κB, MMP-9, and vEGF); decreased the expression of TLR4 pathway (MyD88, TLR4, NF-κB, and HMGB1); attenuated lipid peroxidation; and activated the Nrf2-ARE pathway	Rat model of SAH or ICH	[112, 143–146]
Sulforaphane	5 mg/kg, ip	Activated Nrf2 in modulating microglia function and hematoma clearance via inducing antioxidative defense components	Rat and mice model of ICH	[50]
Sesamin	30 nmol, icv	Sesamin prevented ICH-induced increase of microglial cells in the perihematomal area, accompanied by the activated p44/42 MAPK pathway	Rat model of ICH	[133]
FeTPPS	30 mg/kg, ip	ONOO^− decomposition catalyst; prevented activation of MMP-9 and Hb-induced neurovascular injuries	Rat model of ICH	[31]
Deferoxamine	100 mg/kg, ip	Reduces neuronal death and neurological deficits after ICH in aged rats	Rat model of ICH	[147]
Edaravone	6 mg/kg, SC	Attenuated ICH-induced brain edema, neurologic deficits, and oxidative injury (apurinic/apyrimidinic abasic sites and 8-hydroxyl-2′-deoxyguanosine)	Rat model of ICH	[103]
Edaravone	10 mg/kg, SC	Improved cerebral metabolism around the hematoma by attenuating apoptotic cell death after ICH	Rat model of ICH	[148]
Hydrogen gas	Inhaled, 2.9%	Reduces damage to the blood brain barrier following ICH and improves SBI	Mice model of ICH	[149, 150]
Rosiglitazone	0.5 mg, infused into the hematoma regions	A remarkable decrease in perihematomal levels of PPARγ, MMP-9, BBB permeability, and BWC following minimally invasive surgery for ICH treatment	Rabbits model of ICH	[151]
Minocycline	45 mg/kg, ip	Reduces iron accumulation and inhibits microglia activation contributing to brain damage after ICH via suppressing MMP-9	Rat model of ICH	[152, 153]
Atorvastatin	2, 5, and 10 mg/kg, orally	Decreasing the brain injury and protecting neurons in ICH involving suppression of TNF-α/MMP-9 and upregulation of IL-10	Rat model of ICH	[154, 155]

PQQ, pyrroloquinoline quinine; MMP-9, matrix metallopeptidase 9; TLR4, Toll-like receptor 4; iNOS, inducible nitric oxide synthase; MyD88, myeloid differentiation factor 88; ip, intraperitoneal injection; icv, intracerebroventricular injection; SC, subcutaneous injection.