Estradiol and Tamoxifen produces acute and chronic neuroprotective effects after spinal cord injury

Estradiol (E 2 ) is a multi‐active steroid that may offer neuroprotection via diverse mechanisms of action. Data on the neuroprotective role of E 2 after spinal cord injury (SCI) is still controversial. We hypothesized that continuous E 2 administration will provide beneficial recovery for injured rats at the behavioral, cellular and molecular level. Tamoxifen (TAM) treatment was evaluated in order to reduce possible detrimental effects from E 2 administration. Female ovariectomized Sprague Dawley rats were surgically implanted with E 2 implants or MPP‐dihydrochloride, an Estrogen Receptor α (ER‐α) antagonist, and then injured at the T10 level. Rats treated with E 2 improved locomotor function in three different tests and MPP‐dihydrochloride treatment confirmed that the effects were ER‐α mediated. E 2 treated rats also showed a reduction in reactive oxygen species (ROS), a reduced lesion cavity and an upregulated ER‐α. Rats treated with TAM had a reduced ROS levels and recovered some locomotor activity. Results suggest that E 2 mediates neuroprotection in SCI by improving locomotor function, reducing the extent of the lesion and ROS while TAM administration suggest a safer, alternative treatment for SCI. Sponsored by the MBRS/RISE (R25GM061838), RCMI (G12RR003051 & G12MD007600), NIH/NINDS (NS39405), and MBRS‐SCORE (2S066M8224) programs.