Premarin stimulates estrogen receptor- to protect against traumatic brain injury in male rats*

Premarin (Wyeth-Ayerst Laboratories, Rouse Point, NY) is a widely used compound for estrogen replacement therapy for uterine bleeding in postmenopausal women. The compound is a pH-balanced mixture of conjugated estrogens (WyethAyerst Laboratories, Rouse Point, NY) occurring as sodium salts of water-soluble estrogen sulfate (including estrone, equilin, 17 -dihydroequilenin, 17 -estradiol, equilenin, and 17 -dihydroequilenin) with lactose, sodium citrate, and simethicone binders (1). Premarin, like 17 estradiol, has significant systemic, coronary, and uterine vascular effects (2). A more recent report has shown that Premarin protects against traumatic brain injury by reducing apoptosis in rats after a contusion of the parietal cortex (3). A more recent report has demonstrated that Premarin can act through estrogen receptor (ER)and to protect hippocampal neurons against global ischemia-induced cell death (4). This raises the possibility that Premarin may act through ER to exert their neuroprotection during traumatic brain injury. The purposes of the presented study were: 1) to determine whether the neuroprotective effects of Premarin in a traumatic brain injury model, which produces selective cerebral infarction and apoptosis as well as motor and cognitive dysfunction, can be reduced by a nonselective ER antagonist, ICI 182, 780 (4); and 2) to identify whether the enhanced neurogenesis and angiogenesis and the reduced brain inflammation after Premarin therapy can be attenuated by ICI 182, 780 in this model. Resultantly, the broad-spectrum ERantagonist ICI 182, 780 abolished the neuroprotective effects of Premarin in male rats subjected to traumatic brain injury by reducing neurogenesis, angiogenesis, and brain inflammation.