TABLE 1.

Ferroptosis-associated drugs in treating the acute CNS injuries.

Disease	Drug	Type	Administration Route	Function and Mechanism
Ischemic stroke	Liproxstatin-1 (Lip-1)	Lipid peroxides inhibitor	Intranasal	Attenuated motor function deficits, cognitive impairment; improved neuroscores; reduced infarct volumes in middle cerebral artery occlusion (MACO) mice.
	Ferrostatin-1 (Fer-1)	Lipid peroxides inhibitor	Intranasal	Attenuated neurological deficits and infarct volumes in MACO mice.
	ML351	Inhibitor of 15-lipoxygenase-1	Intravenous	Reduced neurological impairment and infarct volume in MACO mice.
	Amyloid precursor protein ectodomain	Protein stabilizing ferroportin to export iron	Intravenous	Improved neuroscores and infarct volume; prevented iron accumulation in the lesioned hemisphere in MACO mice.
	Ceruloplasmin	Copper regulating iron-mediated transport	Intraperitoneal	Suppressed ischemia-induced hippocampal iron elevation in the lesioned hemisphere in MACO mice.
	Carvacrol	Monoterpenic phenol	Intraperitoneal	Reduced neuronal cell death, increased GPx4 expression in gerbils I/R hippocampal neurons (in vitro); decreased the level of lipid peroxide and MDA, TFR, increased the Fpn1 expression; alleviated neuronal degeneration and memory deficits in I/R gerbils.
	Deferoxamine	Iron chelator	Intraperitoneal	Suppressed the level of MDA.
	Edaravone	Free radical scavenger; A clinically approved drug for treating acute ischemic stroke	Not applicable	Suppressed the accumulation of lipid peroxidation and ROS production; inhibited ferroptosis induced by cystine deprivation, erastin and RSL3 by scavenging radical species in non-neuronal cells (in vitro).
	Tat-linked SelP Peptide	BBB-permeable peptide containing selenocysteine	Intraperitoneal	Reduced infarct volume in rodent MCAO model.
ICH	Ferrostatin-1	Lipid peroxides inhibitor	Intracerebroventricular or intraperitoneal	Prevented lipid ROS, MDA and GPx activity deficit (in vitro); inhibited Hb/ferrous-induced and hemin/hemoglobin-induced neuronal death (in vitro); reduced iron deposition and lipid ROS; diminished injury volume; rescued degenerating neurons, and corrected neurologic deficit in collagenase-induced ICH model; suppressed the level of GPX4; alleviated neuronal dysfunction; moderated brain atrophy and exerted long-term neuroprotective effects in autologous blood infusion model of ICH.
	Liproxstatin-1	Lipid peroxides inhibitor	Intraperitoneal	Inhibited Hb-induced cell death; decreased neurologic deficits and lesion volume; rescued neuronal cells in collagenase-induced ICH model.
	Zileuton/BW B70/BW A4C	Arachidonate 5-lipoxygenase (ALOX5) inhibitors	Not applicable	Inhibited Hb/hemin-induced cell death (in vitro).
	Compound 968	Glutaminase inhibitor	Intraperitoneal	Decreased degenerating neurons.
	Deferoxamine	Iron chelator		Inhibited hemin/hemoglobin-induced neuronal death.
	N-acetylcysteine (NAC)	Glutathione prodrug; Thiol-containing redox modulatory compound	Intraperitoneal	Inhibited hemin/hemoglobin-induced neuronal death (in vitro); increased glutathione, deceased nuclear ALOX5-derived reactice lipid species, reduced neuronal death, improved functional recovery in collagenase-induced mouse model of ICH.
	Trolox	Water soluble lipid peroxidation inhibitor	Not applicable	Inhibited hemin/hemoglobin-induced neuronal death (in vitro).
	U0126	Extracellular-signaling kinase 1/2 (ERK1/2) inhibitor	Not applicable	Inhibited hemin/hemoglobin-induced neuronal death (in vitro).
	(-)-Epicatechin	Brain-permeable flavanol	Orally	Diminished heme oxygenase-1 expression and brain iron deposition via an Nrf2-independent pathway, reduced lesion volume and ameliorated neurologic deficits in collagenase/autologous blood/thrombi-induced ICH model.
	Loxothiazolidine-4-carboxylate (OTC)	Cysteine prodrug	Not applicable	Inhibited hemin-induced neuronal death (in vitro).
	Glutathione ethyl ester	Membrane permeable form of glutathione	Not applicable	Inhibited hemin-induced neuronal death (in vitro).
	Tat SelPep	BBB-permeable peptide containing selenocysteine	Intraperitoneal	Increased GPX4 expression; prevented hemin-induced ferroptosis and preserved cell bodies and neurites of neurons (in vitro); unregulated transcriptional expression of GPX4; inhibited cell death and improved function in collagenase-induced ICH model.
	Selenium	Essential micronutrient	Intracerebroventricular	Diminished cell death and improved functional recovery in a mouse model of ICH.
TBI	Ferrostatin-1	Lipid peroxides inhibitor	Intracerebroventricular	Reduced neuronal death in mechanical stretch-elicited TBI model (in vitro); reduced iron accumulation, neuron degeneration and lesion volume; ameliorated cognitive and motor function deficits in the adult controlled cortical impact injury (CCI) mouse model.
	Triacsin C	Acyl-CoA synthetase long-chain family member 4 (ACSL4) inhibitor	Not applicable	Reduced neuronal cell death in mechanical stretch-elicited TBI model (in vitro).
	Liproxstatin-1	Lipid peroxides inhibitor	Not applicable	Reduced neuronal cell death in mechanical stretch-elicited TBI model (in vitro).
	Baicalein	12/15-lipoxygenase inhibitor	Intraperitoneal	Reduced neuronal cell death in mechanical stretch-elicited TBI model (in vitro); attenuated phosphatidylethanolamine oxidation and improved function in CCI mouse model.
	miR-212-5p agomir	MicroRNAs agomir	Intracerebroventricular	Improved memory and learning in CCI mice.
SCI	Deferoxamine	Iron chelator	Intraperitoneal	Increased xCT, GSH, and GPX4 levels; protected neurons and promoted long-term functional recovery in rat contusion SCI model.
	SRS 16-86	Small molecule ferroptosis specific inhibitor	Intraperitoneal	Upregulated GPX4, GSH and xCT levels; down-regulated the expression of 4HNE; increased neuronal survival and promoted functional recovery in rat contusion SCI model.