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

Abstract

Estradiol (E2) is a multi‐active steroid that may offer neuroprotection via diverse mechanisms of action. Data on the neuroprotective role of E2 after spinal cord injury (SCI) is still controversial. We hypothesized that continuous E2 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 E2 administration. Female ovariectomized Sprague Dawley rats were surgically implanted with E2 implants or MPP‐dihydrochloride, an Estrogen Receptor α (ER‐α) antagonist, and then injured at the T10 level. Rats treated with E2 improved locomotor function in three different tests and MPP‐dihydrochloride treatment confirmed that the effects were ER‐α mediated. E2 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 E2 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.