Protective Effects of Estradiol and Dihydrotestosterone following Spinal Cord Injury

Abstract

Spinal cord injury (SCI) results in lesions that destroy tissue and disrupt spinal tracts, producing deficits in locomotor and autonomic function. We previously demonstrated that motoneurons and the muscles they innervate show pronounced atrophy after SCI, and these changes are prevented by treatment with testosterone. Here, we assessed whether the testosterone active metabolites estradiol and dihydrotestosterone have similar protective effects after SCI. Young adult female rats received either sham or T9 spinal cord contusion injuries and were treated with estradiol, dihydrotestosterone, both, or nothing via Silastic capsules. Basso-Beattie-Bresnahan locomotor testing was performed weekly and voiding behavior was assessed at 3 weeks post-injury. Four weeks after SCI, lesion volume and tissue sparing, quadriceps muscle fiber cross-sectional area, and motoneuron dendritic morphology were assessed. Spontaneous locomotor behavior improved after SCI, but hormone treatments had no effect. Voiding behavior was disrupted after SCI, but was significantly improved by treatment with either estradiol or dihydrotestosterone; combined treatment was maximally effective. Treatment with estradiol reduced lesion volume, but dihydrotestosterone alone and estradiol combined with dihydrotestosterone were ineffective. SCI-induced decreases in motoneuron dendritic length were attenuated by all hormone treatments. SCI-induced reductions in muscle fiber cross-sectional areas were prevented by treatment with either dihydrotestosterone or estradiol combined with dihydrotestosterone, but estradiol treatment was ineffective. These findings suggest that deficits in micturition and regressive changes in motoneuron and muscle morphology seen after SCI are ameliorated by treatment with estradiol or dihydrotestosterone, further supporting a role for steroid hormones as neurotherapeutic agents in the injured nervous system.