Table 3.
MTAs in TBI models.
| Mitochondria-targeted antioxidants/bioactive component | Models/clinical trials | Dosage | Effects/mechanism | Reference |
|---|---|---|---|---|
| SkQR1 | Rat model by brain surgery | 100 nmol/kg; intraperitoneal injection | (1) Decreased the neurological deficit (2) Lowered the volume of the lesion in the brain cortex (3) Decreased mitochondrial ROS and GSK-3β activity |
[106] |
| Rat model of focal one-sided TBI | 250 nmol/kg; intraperitoneal injection | (1) Rescued the disruptions of limb functions (2) Increased survivability of neurons (3) Decreased astroglial expression and infiltration with segmented neutrophils (4) Beneficial effects are dependent on the reduction of mitochondrial reactive oxygen species |
[107] | |
|
| ||||
| XJB-5-131 | Rat CCI model after TBI | 10 mg/kg bodyweight; intravenous injection | (1) Protected brain thiols, GSH and PSH, oxidized by TBI (2) Decreased caspase 3/7 activity and attenuated apoptotic neuronal death (3) Scavenged the electrons leaking from electron carriers |
[108] |
|
| ||||
| Mito-TEMPO | Isolated MCAs from rats with traumatic injury | 30 nmol in the vessel chamber | (1) Alleviated myogenic constriction (2) Scavenged H2O2 (PEG-catalase) by blocking both BKCa channels and TRPV4 channels |
[109] |
|
| ||||
| SS-31 | Marmarou's weight drop model of TBI | 5 mg/kg; intraperitoneal administration | (1) Rescued mitochondrial dysfunction, and alleviated secondary brain injury (2) Decreased ROS, malondialdehyde, and cytochrome c release and prevented the decline of SOD activity (3) Attenuated neurological deficits, brain water content, DNA damage, and neural apoptosis |
[77] |
|
| ||||
| MitoQ | Marmarou's weight drop model | 4 mg/kg; intraperitoneal administration | (1) Alleviated neurological deficits and brain edema and inhibited cortical neuronal apoptosis (2) Increased the activity of SOD and GPx and decreased MDA level (3) Reduced Bax translocation to mitochondria and cytochrome c release into the cytosol (4) Accelerated the Nrf2 nuclear translocation and upregulated the Nrf2 downstream proteins, including HO-1 and Nqo1 |
[110] |
Notes: Bax: (Bcl-2)-associated X; BKCa: big conductance Ca2+-activated K+; CCI: chronic constriction injury; GPx: glutathione peroxidase; GSH: glutathione; GSK-3β: glycogen synthase kinase-3β; HO-1: heme oxygenase-1; MCAs: middle cerebral arteries; MDA: malondialdehyde; Nqo1: quinone oxidoreductase 1; Nrf2: nuclear factor erythroid 2; PEG-catalase: polyethylene glycol; PSH: protein thiols; SOD: superoxide dismutase; TBI: traumatic brain injury.