Time Course of Mitochondrial Antioxidant Markers in a Preclinical Model of Severe Penetrating Traumatic Brain Injury

Traumatic brain injury (TBI) results from external mechanical forces exerted on the brain, triggering secondary injuries due to cellular excitotoxicity. A key indicator of damage is mitochondrial dysfunction, which is associated with elevated free radicals and disrupted redox balance following TBI. However, the temporal changes in mitochondrial redox homeostasis after penetrating TBI (PTBI) have not been thoroughly examined. This study aimed to investigate redox alterations from 30 min to two-weeks post-injury in adult male Sprague Dawley rats that experienced either PTBI or a Sham craniectomy. Redox parameters were measured at several points: 30 min, 3 h, 6 h, 24 h, 3 d, 7 d, and 14 d post-injury. Mitochondrial samples from the injury core and perilesional areas exhibited significant elevations in protein modifications including 3-nitrotyrosine (3-NT) and protein carbonyl (PC) adducts (14–53%, vs. Sham). In parallel, antioxidants such as glutathione, NADPH, peroxiredoxin-3 (PRX-3), thioredoxin-2 (TRX-2), and superoxide dismutase 2 (SOD2) were significantly depleted (20–80%, vs. Sham). In contrast, catalase (CAT) expression showed a significant increase (45–75%, vs. Sham). These findings indicate a notable imbalance in redox parameters over the two-week post-PTBI period suggesting that the therapeutic window to employ antioxidant therapy extends well beyond 24 h post-TBI.