Effects of Clobetasol in an Aging Mouse Model of Spinal Cord Hemisection

Spinal cord injury leads to permanent neurological deficits, and aging further diminishes the plasticity and regenerative responses required for recovery. Activation of the Sonic hedgehog (Shh) pathway through the receptor Smoothened (Smo) has been proposed as a potential strategy to promote repair, and clobetasol, a potent glucocorticoid, has been identified as a pharmacological Smo agonist. However, the possible restorative effect of Smo agonists has never been studied during aging. Here, the effects of clobetasol treatment have been investigated in aging mice following spinal cord hemisection. Animals received weekly systemic injections of clobetasol or vehicle and were monitored for 11 weeks using the Basso Mouse Scale and open field test, followed by post-mortem histological analysis. Vehicle-treated mice exhibited a modest spontaneous recovery of locomotor function, whereas clobetasol-treated mice failed to improve and displayed significantly worse motor performance. Histological evaluation revealed reduced synaptic density in clobetasol-treated mice. Moreover, microglia/macrophage reaction was increased in vehicle-treated injured mice but suppressed by clobetasol, consistent with glucocorticoid-mediated inhibition of inflammatory responses. Together, these findings indicate that in aged animals clobetasol administration does not enhance plasticity or promote recovery but instead exacerbates synaptic loss and functional deficits. These results underscore the importance of age as a determinant of therapeutic efficacy after spinal cord injury.