Gender Differences in Spinal Cord Injury Are Not Estrogen-Dependent

Abstract

Recent attention has been given to gender differences in neurotrauma, and the anecdotal suggestion is that females have better outcomes than males, suggesting that circulating levels of estrogen (E(2)) may be neuroprotective. In order to address this issue, both young adult male and ovariectomized female rats were subjected to a T10 spinal cord injury (SCI), and E2 levels were maintained at chronic, constant circulating levels. Animals were clinically evaluated for locomotor changes using the Basso-Beattie-Bresnahan (BBB) scoring system. Morphologic differences were evaluated with unbiased stereology. Data analysis failed to reveal any significant benefit for the E2 therapy in either males or females. We did find a non-estrogen-dependent difference between male and female rats in length of injury, and percent of spared tissue, with female outcomes more favorable. These results suggest that E(2) does not provide a viable therapy following SCI.

Tamoxifen and estradiol improved locomotor function and increased spared tissue in rats after spinal cord injury: Their antioxidant effect and role of estrogen receptor alpha

“…Moreover, continuous administration of estradiol at low physiological doses (Samantaray et al, 2011) stimulates a greater neuroprotective response than that seen in normal cycling rats. These findings suggest that maintaining constant levels of estradiol promotes a greater neuroprotective effect, as well as some locomotor recovery, and these results are in contrast to some published studies (Baker and Hagg, 2005; Swartz et al, 2007). However, differences in the doses of estradiol used, regimen of infusion, and mode of administration have expanded the array of results reported (Elkabes and Nicot, 2014).…”

“…Swartz et al 2007 showed that exposure to estradiol at low (28.2 pg/mL) or high (72 pg/mL) doses did not improve locomotor recovery in injured female rats. Baker & Haggs in 2005 concluded that the level of estradiol at different stages of the estrous cycle did not affect the functional outcome after SCI.…”

Effects of Chronic Restraint Stress and 17-β-Estradiol Replacement on Oxidative Stress in the Spinal Cord of Ovariectomized Female Rats

“…Thus, in addition to their neuroprotective effects, in some circumstances estrogens may be neurotoxic or ineffective as neuroprotector agents. For example, pre-treatment with estradiol exacerbates ischaemic oxidative damage [48] and has no effect on spinal cord injury [49]. Furthermore, a recent review [50] suggested that estradiol is effective in the prevention of disease, but not as a treatment for existing diseases.…”

Adenosine A1 receptor agonists reduce hyperalgesia after spinal cord injury in rats

“…Swartz et al 14 reported that the outcome of motor function after SCI in female rats was better than that in males. They also reported that the difference of outcome was not dependent on estrogen.…”