Estrogen-Related Gender Difference in Survival Rate and Cortical Blood Flow After Impact-Acceleration Head Injury in Rats

Abstract

While a number of laboratories have begun to examine gender differences in outcome following experimental stroke, little is known about the relative response of male and female brains to traumatic injury. In the following series of experiments, we used the Marmarou impact-acceleration head injury model (with a 500-g, 1.5-m weight drop) to compare the pathophysiological responses of male and female rats to closed-head injury. Cortical blood flow (CBF; laser-doppler flowmetry), mean arterial blood pressure (MAP), blood gas levels, blood pH, and body temperature were measured preinjury and at regular intervals postinjury. Acute survival was assessed 1 h after injury. The role of estrogen in the observed gender differences was assessed by examining these physiological measures after injury in ovariectomized females, with or without 17beta-estradiol replacement, and in intact males, with or without exogenous 17beta-estradiol administration. In the first experiment, significantly more females (100%) survived the acute injury period (60 min) after injury than did males (72%). Survival appeared related to the magnitude and persistence of the posttraumatic drop in MAP. In a second experiment, females showed a less dramatic reduction in and better recovery of CBF than males. The gender difference in CBF was paralleled to some degree by differences in the pattern of MAP changes after injury. Differences in body weight, blood gas levels, or blood pH did not account for the gender difference in CBF. Postinjury CBF was higher in female and male rats given 2 weeks of daily 17beta-estradiol injections prior to injury compared to those given the vehicle only. However, 17beta-estradiol administration did not alter MAP, suggesting that the gender difference in CBF was not strictly due to MAP changes. Our findings suggest that estrogen plays a role in maintaining adequate cerebral perfusion in the acute period following closed-head injury. This protective mechanism may underlie the gender difference in acute survival observed in this study, and may help explain observations of better outcome in females than in males after brain injury. We conclude that CBF preservation is one mechanism by which estrogen is neuroprotective following traumatic brain injury. We hypothesize, based upon known effects of estrogen, that the beneficial microvascular effects of estrogen most likely involve a combination of endothelial nitric oxide synthase induction and an antioxidant effect.

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

“…Hormonal levels were not determined in that study and it is unknown what the exact levels of the various gonadal hormones were in that particular experiment. Roof and Hall (2001) reported smaller reductions in cerebral blood flow following TBI with 17␤-estradiol treatment in female rats compared to males. Recently, a decrease in contusion volume after TBI was shown in intact females versus males or ovariectomized females (Bramlett and Dietrich, 2001).…”

Gender-related differences in recovery of locomotor function after spinal cord injury in mice

“…[1][2][3][4] Hall et al 2 showed that 24 h after incomplete ischemia produced by temporary unilateral carotid occlusion, male gerbils demonstrated significantly more neuronal loss in the cerebral cortex and the CA1 of the hippocampus than did females. Alkayed et al 5 reported that using a model of temporary middle cerebral artery (MCA) occlusion both Wistar and hypertensive female rats had smaller infarcts in the cortex and caudateputamen than did males of the same strain.…”

“…7,8 Similiarly, after a closed head injury, 100% of female rats, as compared to 75% of the males, survived. 3 Roof et al 9 reported that male rats were significantly impaired in their performance on the Morris water maze task after electrolytic lesion of cortex, while lesioned females performed the task as well as did noninjured controls.…”

Effects of Combined Oral Conjugated Estrogens and Medroxyprogesterone Acetate on Brain Infarction Size after Experimental Stroke in Rat

“…Like estrogen, progesterone has been shown to be protective in models of traumatic brain injury (Bramlett and Dietrich, 2001;Stein, 2001;Wright et al, 2001), but variable effects have been noted after ischemic brain injury (Roof and Hall, 2000;Stein and Hoffman, 2003). Early studies of unopposed estrogen replacement in women report a reduction in risk for cardiovascular disease (Hurn and Brass, 2003).…”