Table 1.
Summary of literature in sex differences in mitochondrial dysfunction following TBI.
| Summary of Sex Differences in Mitochondrial Bioenergetic Function after TBI | ||||
|---|---|---|---|---|
| Reference | Species (Age; Alteration) | TBI Model and Severity | Male Result | Female Result |
| Greco et al. (2020) | Rat (adult) | CCI; severe (2 mm depth) | Decreased State III respiration and RCR compared to sham. | Decreased State III and State V respiration, but no change in RCR compared to sham. |
| Robertson et al. (2006) | Rat (adult; OVX) | CCI; moderate-severe (1.5 mm depth) | - | Progesterone (25 ng/ml) improved RCR after CCI relative to sham. |
| Robertson and Saraswati (2015) | Rat (PND 17–21) | CCI; moderate-severe (1.5 mm depth) | Progesterone (10 mg/kg) improved RCR after CCI similar to sham. | CCI did not significantly reduce RCR compared to sham; progesterone treatment did not significantly improve RCR compared to the other groups. |
| Carteri et al. (2019) | Mouse (adult) | CCI; severe (2 mm depth) | Testosterone (15 mg/kg) improved State III respiration (CI) and maximum OxPHOS after CCI similar to sham; Testosterone improved ΔΨm after CCI similar to sham. | - |
| CCI = controlled cortical impact; State III respiration = glutamate, malate, and ADP (Greco et al., 2020), pyruvate, malate, glutamate, and ADP (Carteri et al., 2019); RCR = (State III/State IV respiration) a general marker of mitochondrial health and coupling ability; OxPHOS = Carteri et al., 2019 defined it as maximal oxidative phosphorylation capacity after additions of pyruvate, malate, glutamate, and succinate in the presence of saturating ADP; ΔΨm = mitochondrial membrane potential. | ||||
| Summary of Sex differences in Mitochondrial Excitotoxicity, Oxidative Stress, and Lipid Peroxidation After TBI | ||||
| Reference | Species (Age; Alteration) | TBI Model and Severity | Male Result | Female Result |
| Greco et al. (2020) | Rat (adult) | CCI; severe (2 mm depth) | Increased peroxide production after CCI similar to sham. | No change in peroxide production after CCI compared to sham. |
| Robertson and Saraswati (2015) | Rat (PND 17–21) | CCI; moderate-severe (1.5 mm depth) | Progesterone (10 mg/kg) prevented CCI-induced reduction in glutathione compared to uninjured control; uninjured male mitochondria had significantly lower levels of glutathione than uninjured female mitochondria. | Progesterone did not prevent CCI-induced glutathione reduction in brain mitochondria after injury compared to uninjured control; mitochondria from uninjured females had higher glutathione levels than that of uninjured males. |
| Carteri et al. (2019) | Mouse (adult) | CCI; severe (2 mm depth) | Testosterone (15 mg/kg) improved baseline peroxide production after CCI similar to sham; Testosterone attenuated peroxide production after respiratory substrate administrations, but was still increased compared to sham; Testosterone reduced total ROS levels similar to sham. | - |
| CCI = controlled cortical impact; ROS = reactive oxygen species; GCS = Glasgow Coma Scale; CSF = cerebrospinal fluid. | ||||
| Summary of Sex Differences in Glucose Metabolism after TBI | ||||
| Reference | Species (Age; Alteration) | TBI Model and Severity | Male Result | Female Result |
| Greco et al. (2020) | Rat (adult) | CCI; severe (2 mm depth) | Exogenous glucose administration during both the hyper- and hypometabolic states after CCI worsened mitochondrial RCR similar to vehicle CCI. | Exogenous glucose administration during hypometabolic state after CCI worsened mitochondrial RCR compared to sham and vehicle CCI; No significant impairment in RCR with glucose administration during hypermetabolic state similar to sham and vehicle CCI. |
CCI = controlled cortical impact; RCR = (State III/State IV respiration) a general marker of mitochondrial health and coupling ability; hypermetabolic state = 0–3 h post-CCI; hypometabolic state = 6–9 h post-CCI (Greco et al., 2020).