Neuroprotective Profile of Dexpanthenol in Traumatic Spinal Cord Injury: A Focus on the Inhibition of Ferroptotic Cell Death.

Abstract

Introduction: Traumatic spinal cord injury (TSCI) is a catastrophic insult to the central nervous system (CNS) and often leaves patients with profound, long-term neurological disability. In this study, we evaluated whether dexpanthenol, a vitamin B5 precursor, exerts neuroprotective effects in a rat model of TSCI. We also sought to clarify the mechanisms that might account for any observed benefit, focusing on pathways related to apoptosis, inflammation, oxidative stress, and ferroptosis.

Methods: We used Wistar albino rats and allocated them into four groups: Control, Sham, Trauma, and Dexpanthenol. Animals in the sham group underwent laminectomy alone. In contrast, rats in the trauma and dexpanthenol groups received a standardized contusion injury created by dropping a 10 g weight from 10 cm onto the exposed spinal cord. Immediately after injury, we administered dexpanthenol intraperitoneally (i.p.) to the treatment group. Neurological function was evaluated 24 h later using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. Biochemical analyses were performed on tissue samples to measure markers of apoptosis (Caspase-3), inflammation (Myeloperoxidase, MPO), lipid peroxidation (Malondialdehyde, MDA), oxidative stress (Xanthine Oxidase, XO, Catalase, CAT), and ferroptosis (Glutathione, GSH, Glutathione Peroxidase 4, GPX4, Acyl-CoA Synthetase Long Chain Family Member 4, ACSL4, and Solute Carrier Family 7 Member 11, SLC7A11). Moreover, we prepared hematoxylin and eosin (H&E) stained sections and carried out a semi-quantitative histopathological evaluation based on these slides.

Results: Relative to the sham condition, spinal cord contusion produced a clear functional deterioration, with BBB locomotor scores dropping sharply and histopathological injury becoming more pronounced. In parallel, the trauma group showed substantial biochemical increases in caspase-3, MPO, MDA, XO, and ACSL4. In contrast, antioxidant and ferroptosis-related defenses were suppressed after injury, as reflected by significantly lower CAT, GSH, GPX4, and SLC7A11 levels. Administration of dexpanthenol shifted this profile. Animals receiving treatment performed better on the BBB scale than untreated trauma rats, indicating a significant recovery of neurological function. Consistently, tissue damage on histology was attenuated, pro-apoptotic and pro-oxidant markers (caspase-3, MPO, MDA, XO, and ACSL4) were reduced, and the depleted protective factors (CAT, GSH, GPX4, and SLC7A11) were brought back toward baseline in a statistically significant manner.

Discussion: The restoration of antioxidant defenses and the specific inhibition of lipid peroxidation markers suggest that dexpanthenol's efficacy extends beyond general anti-inflammatory effects. By targeting ferroptosis-associated molecular changes via the preservation of the GPX4/GSH axis, dexpanthenol addresses a fundamental mechanism of secondary neuronal death. These findings highlight the therapeutic relevance of stabilizing membrane lipids and cellular energetics in the acute phase of neurotrauma.

Conclusion: Taken together, our data suggest that dexpanthenol provides significant protection in the setting of TSCI. The benefit seems to arise from a multi-pronged profile: it inhibits apoptosis and inflammation, limits oxidative damage, and attenuates key components of the ferroptotic cascade. In light of these converging effects, dexpanthenol warrants further investigation as a candidate therapy for TSCI.