Journal of neurotrauma
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Journal of neurotrauma · Mar 2024
Protective effects of Hinokitiol on neuronal ferroptosis by activating the KEAP1/NRF-2/HO-1 pathway in traumatic brain injury.
In this study, we investigated the effects of hinokitiol, a small-molecule natural compound, against neuronal ferroptosis after traumatic brain injury (TBI). A controlled cortical impact (CCI) mouse model and excess glutamate-treated HT-22 cells were used to study the effects of hinokitiol on TBI. Hinokitiol mitigated TBI brain tissue lesions and significantly improved neurological function. ⋯ Mechanistically, hinokitiol upregulated heme oxygenase-1 (HO-1) expression, promoted nuclear factor-erythroid factor 2-related factor 2 (Nrf2) nuclear translocation, and inhibited the activation of microglia and astrocyte after TBI. These results suggest that hinokitiol has neuroprotective effects on rescuing cells from TBI-induced neuronal ferroptosis. In summary, hinokitiol is a potential therapeutic candidate for TBI by activating the Nrf2/Keap1/HO-1 signaling pathway.
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Journal of neurotrauma · Mar 2024
Delayed administration of an angiotensin II type 2 receptor agonist promotes functional recovery of the brain and heart after traumatic brain injury.
Cardiac injury is a common complication following traumatic brain injury (TBI) that can lead to poor clinical outcomes. Angiotensin II type 2 receptor (AT2R) activation exerts protective roles in the brain and heart, yet its potential impact on TBI or TBI-induced cardiac deficits remains elusive. The goal of this study was to investigate the influence of AT2R activation on recovery after TBI-induced cognitive and cardiac injury using the selective nonpeptide AT2R agonist compound 21 (C21). ⋯ Meanwhile, C21 benefited cardiac function, as identified by increased left ventricular ejection fraction 1 month after TBI. In addition, C21 alleviated TBI-induced cardiac hypertrophy and fibrosis; however, blood pressure was not affected. Our results demonstrate that AT2R activation ameliorates TBI-induced neurological and cardiac deficits.
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The long-term effects of exposure to blast overpressure are an important health concern in military personnel. Increase in amyloid beta (Aβ) has been documented after non-blast traumatic brain injury (TBI) and may contribute to neuropathology and an increased risk for Alzheimer's disease. We have shown that Aβ levels decrease following exposure to a low-intensity blast overpressure event. ⋯ Additionally, significant increases in brain levels of the endothelial transporter, low-density related protein 1 (LRP1), and enhancement in co-localization of aquaporin-4 (AQP4) to perivascular astrocytic end-feet were observed 24 h after blast exposure. These findings suggest that exposure to low-intensity blast may enhance endothelial clearance of Aβ by LRP1-mediated transcytosis and alter AQP4-aided glymphatic clearance. Collectively, the data demonstrate that low-intensity blast alters enzymatic, transvascular, and perivascular clearance of Aβ.
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Journal of neurotrauma · Feb 2024
Review Meta AnalysisSurgical Outcomes in Post-Traumatic Temporal Lobe Epilepsy: A Systematic Review and Meta-Analysis.
Epilepsy surgery provides excellent benefits in post-traumatic epilepsy of the temporal lobe (PTE-TL), but outcomes relative to non-traumatic epilepsy of the temporal lobe (NTE-TL) are less favorable. Large well-designed studies are recommended to further clarify the role of epilepsy surgery in PTE. It is unclear whether epilepsy surgery outcomes in PTE are as robust as described for drug resistant epilepsy (DRE) in general. ⋯ Of 3669 articles that reported surgical outcomes in epilepsy, nine studies (n = 886) were identified that reported outcomes for both PTE-TL (n = 219) and NTE-TL (n = 667). The weighted proportion of favorable outcomes (Engel Class I) were high for both PTE-TL (70.1%, 95% CI 61.9%-78.3%) and NTE-TL (75.2%, 95% CI 69.4%-80.2%). Patients with PTE-TL were at greater risk of unfavorable (Engel Class II-IV) outcomes (relative risk 1.36, 95% CI 1.04-1.78) compared with NTE-TL.