There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neu-roprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inlfammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphor-ylation of Aktvia its threonine 308 phosphorylation site. Phosphorylation at the threonine 308 site is one of several sites responsible for activating Akt and enabling the protein kinase to carry out its neuroprotective effects. To assess the effects of progesterone on Akt phosphorylation, C57BL/6 mice were treated with progesterone (8 mg/kg) at 1 (intraperitonally), 6, 24, and 48 hours (subcutaneously) post closed-skull traumatic brain injury. The hippocampus was harvest-ed at 72 hours post injury and prepared for western blot analysis. Traumatic brain injury caused a signiifcant decrease in Akt phosphorylation compared to sham operation. However, mice treat-ed with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our ifndings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.

There is currently no standard pharmacological treatment for spinal cord injury. Here, we suggest that progesterone, a steroid hormone, may be a promising therapeutical candidate as it is already for traumatic brain injury, where it has reached phase II clinical trials. We rely on previous works showing anti-inflammatory, neuroprotective and promyelinating roles for progesterone after spinal cord injury and in our recent paper, in which we demonstrate that progesterone dimin-ishes lesion, preserves white matter integrity and improves locomotor recovery in a clinically relevant model of spinal cord lesion.

Progestogens and early pregnancy:prevention and treatment

雌孕激素替代治疗对大鼠心血管功能的保护作用

Objective To observe the change of the cardiovascular effect of estrogen replacement therapy in rat after treated with progesterone. Method Thirty female rates were randomly divided into three groups: group A: ovarietcomy; group B: ovariectomy with estrogen replacement therapy and group C: ovariectomy with estrogen and progesterone replacement therapy. The estrogen receptors (ER) in the artery of the rat were measured and the serum level of nitric oxide (NO), endothelin 1 (ET 1), prostacyclin (PGF1a) and thromboxane (TXB2) were detected 2 months later. Results (1) There was no apparent difference in ER expression, serum NO and PGF1a level between group C and group B; these index of group B and C were higher than those of group A; (2) there was no significant difference in blood viscosity, the congregate index of red blood cell and platelet adhesiveness rate between group B and C; these index of group B and C were lower than those of group A. Conclusion Estrogen replacement therapy adding progesterone makes no influence on arterial ER expression, hemorheology index and regulation of estrogen to cardiovascular cytokines generation. It suggested that estrogen combined with progesterone replacement therapy could be a safe and effective method to prevent coronary heart disease.

The potential role of progesterone during pregnancy as an induction of infantile hemangioma

Infantile hemangioma (IH) is one of the most common benign tumors in infants characterized by occurrence within a few weeks after birth,rapid growth during the first year and spontaneous involution over a period of several years.Despite the high incidence rate of 5％-10％ in infants of mixed European descent,detailed pathogenesis of IH remains elusive.Recent studies have indicated multipotential stem cells derived from hemangioma tissue (HemSCs) could recapitulate human infantile hemangioma in immunodeficient mice.Considering the effect of progesterone on regulation of cytokines and growth factors in endometrium as well as the inhibition of immune response,using progesterone during pregnancy might help the HemSCs escape from the immune response and reside in the tissue of embryo by the aid of increased MMPs and decreased TIMPs,then proliferation was stimulated by increased growth factors like VEGF and bFGF.Thus,IH is potentially produced.Supported by National Natural Science Foundation of China (81070846).

黄体酮对活化小胶质细胞TNF-α与IL-1β分泌的影响

Objective Inflammatory cytokines play important roles in the pathophysiology of cerebral infarction and other central nervous system diseases.This study was designed to investigate the influence of progesterone on lipopolysaccharide-induced expression of tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) in primary cultured microglia.Methods Microglia were obtained from cerebral cortexes of neonatal Sprague Dawley rats.Microglia were separated,purificated, cultured and activated.ELISA was used to detect the level of TNF-α, IL-1β in supernate fluid before and after induced with lipopolysaccharide (LPS) or influenced by progesterone.Results LPS strongly induced the expression of TNF-α, IL-1β in microglia from cerebral cortexes.Progesterone inhibited the expression of TNF-α, IL-1β.Conclusion progesterone significantly reduced the expression of inflammatory factors generated by microglia and inhibited the activation of microglia in vitro.