Andrabi Syed Suhail, Parvez Suhel, Tabassum Heena
Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
J Environ Pathol Toxicol Oncol. 2017;36(3):191-205. doi: 10.1615/JEnvironPatholToxicolOncol.2017017156.
Progesterone (P4), a well-known neurosteroid, is produced by ovaries and placenta in females and by adrenal glands in both sexes. Progesterone is also synthesized by central nervous system (CNS) tissues to perform various vital neurological functions in the brain. Apart from performing crucial reproductive functions, it also plays a pivotal role in neurogenesis, regeneration, cognition, mood, inflammation, and myelination in the CNS. A substantial body of experimental evidence from animal models documents the neuroprotective role of P4 in various CNS injury models, including ischemic stroke. Extensive data have revealed that P4 elicits neuroprotection through multiple mechanisms and systems in an integrated manner to prevent neuronal and glial damage, thus reducing mortality and morbidity. Progesterone has been described as safe for use at the clinical level through different routes in several studies. Data regarding the neuroprotective role of P4 in ischemic stroke are of great interest due to their potential clinical implications. In this review, we succinctly discuss the biosynthesis of P4 and distribution of P4 receptors (PRs) in the brain. We summarize our work on the general mechanisms of P4 mediated via the modulation of different PR and neurotransmitters. Finally, we describe the neuroprotective mechanisms of P4 in ischemic stroke models and related clinical prospects.
孕酮（P4）是一种著名的神经甾体，在女性体内由卵巢和胎盘产生，在两性体内均由肾上腺产生。中枢神经系统（CNS）组织也能合成孕酮，以在大脑中执行各种重要的神经功能。除了执行关键的生殖功能外，它在CNS的神经发生、再生、认知、情绪、炎症和髓鞘形成中也起着关键作用。来自动物模型的大量实验证据证明了P4在包括缺血性中风在内的各种CNS损伤模型中的神经保护作用。大量数据表明，P4通过多种机制和系统以综合方式引发神经保护作用，以防止神经元和神经胶质损伤，从而降低死亡率和发病率。在多项研究中，已表明孕酮通过不同途径在临床水平使用是安全的。由于P4在缺血性中风中的神经保护作用具有潜在的临床意义，因此相关数据备受关注。在本综述中，我们简要讨论了P4的生物合成以及P4受体（PRs）在大脑中的分布。我们总结了我们关于P4通过调节不同PR和神经递质介导的一般机制的研究工作。最后，我们描述了P4在缺血性中风模型中的神经保护机制及相关临床前景。
