Postinjury administration of 17β-estradiol induces protection in the gray and white matter with associated functional recovery after cervical spinal cord injury in male rats

Abstract

The majority of spinal cord injuries (SCIs) in the clinic occur at the lower cervical levels, resulting in both white and gray matter disruption. In contrast, most experimental models of SCI in rodents induce damage in the thoracic cord, resulting primarily in white matter disruption. To address this disparity, experimental cervical SCI models have been developed. Thus, we used a recently characterized model of cervical hemicontusion SCI in adult male rats to assess the potential therapeutic effect of post-SCI administration of 17β-estradiol. Rats received a hemicontusion at the level of the fifth cervical vertebra (C5) followed by administration of 17β-estradiol via a slow release pellet (0.5 or 5.0 mg/pellet) beginning at 30 minutes post-SCI. Behavioral evaluation of skilled and unskilled forelimb function and locomotor function were conducted for 7 weeks after SCI. Upon conclusion of the behavioral assessments, spinal cords were collected and histochemistry and stereology were conducted to evaluate the effect of treatment on the lesion characteristics. We found that post-SCI administration of 17β-estradiol decreased neuronal loss in the ventral horn, decreased reactive astrogliosis, decreased the immune response, and increased white mater sparing at the lesion epicenter. Additionally, post-SCI administration of 17β-estradiol improved skilled forelimb function and locomotor function. Taken together, these data suggest that post-SCI administration of 17β-estradiol protected both the gray and white matter in cervical SCI. Moreover, this treatment improved function on skilled motor tasks that involve both gray and white matter components, suggesting that this is likely a highly clinically relevant protective strategy.