Systemic administration of 17b-estradiol reduces apoptotic cell death and improves functional recovery following traumatic spinal cord injury in rats

Recent evidence indicates that estrogen exerts neuroprotective effects in both brain injury and neu-rodegenerative diseases. We examined the protective effect of estrogen on functional recovery after spinal cord injury (SCI) in rats. 17b-estradiol (3, 100, or 300 mg/kg) was administered intravenously 1–2 h prior to injury (pre-treatment), and animals were then subjected to a mild, weight-drop spinal cord contusion injury. Estradiol treatment significantly improved hind limb motor function as de-termined by the Basso-Beattie-Bresnahan (BBB) locomotor open field behavioral rating test. Fif-teen to 30 days after SCI, BBB scores were significantly higher in estradiol-treated (100 mg/kg) rats when compared to vehicle-treated rats. Morphological analysis showed that lesion sizes increased progressively in either vehicle-treated or 17b-estradiol-treated spinal cords. However, in response to treatment with 17b-estradiol, the lesion size was significantly reduced 18–28 days after SCI when compared to vehicle-treated controls. Terminal deoxynucleotidyl transferase-mediated UTP nick-end labeling (TUNEL) staining and DNA gel electrophoresis revealed that apoptotic cell death peaked 24–48 h after injury. Also, SCI induced a marked increase in activated caspase-3 in the spinal cord, evident by 4 h after injury. However, administration of 17b-estradiol significantly reduced the SCI