Tibolone Administration Is Associated with Enhanced Motor Recovery and Decreased Cell-Specific NOX2 and NOX4 Immunoreactivity in a Rat Model of Traumatic Spinal Cord Injury

Background/Objectives: This study aimed to investigate the effect of tibolone (TIB) on the expression of the NOX2 and NOX4 isoforms and their co-localization in neurons and astrocytes using an animal model of spinal cord injury (SCI). Methods: Male Sprague Dawley rats were subjected to contusive SCI at T9 and treated with TIB (1 or 2.5 mg/kg/day). The expression of NOX2 and NOX4, and their co-localization in neurons and astrocytes, were evaluated at 3, 7, and 15 days post-SCI. Oxidative stress markers and motor recovery were also assessed. Results: SCI induced a time-dependent increase in NOX2 protein expression at 15 days compared to 3 days (0.192 ± 0.012 vs. 0.013 ± 0.0007) and in NOX4 protein expression (0.027 ± 0.002 vs. 0.958 ± 0.088), displaying differential cell-specific localization patterns in neurons and astrocytes across time points. TIB treatment significantly attenuated SCI-induced oxidative stress (15,391.8 ± 1047.6 vs. 21,264.4 ± 2669.8) and decreased NOX2 and NOX4 co-localization in both neurons and astrocytes in a dose- and time-dependent manner. Furthermore, TIB-treated animals exhibited a modest but significant restoration of motor function at 15 days post-SCI. Conclusions: Our findings indicate that TIB administration reduces oxidative stress, modifies NOX2 and NOX4 immunoreactivity patterns in neurons and astrocytes, and promotes partial functional recovery following SCI.