Department of Pharmacology and Toxicology, University of Kansas, School of Pharmacy, 1251 Wescoe Hall Drive, Malott Hall 5044, Lawrence, KS 66045, USA.
Curr Med Chem. 2009;16(34):4593-600. doi: 10.2174/092986709789760779.
In stroke research, a significant focus is to develop therapeutic strategies that prevent neuronal death and improve recovery. Yet, few successful therapeutic strategies have emerged. Hypoxia-inducible factor 1 (HIF-1) is a key regulator in hypoxia. It has been suggested to be an important player in neurological outcomes following ischemic stroke due to the functions of its downstream genes. These include genes that promote glucose metabolism, angiogenesis, erythropoiesis, and cell survival. Many lines of evidence have shown that HIF-1 is induced in ischemic brains. Importantly, it seems that HIF-1 is primarily induced in the salvageable tissue of an ischemic brain, penumbra. However, the effect of HIF-1 on neuronal tissue injuries is still debatable based on evidence from in vitro and preclinical studies. Furthermore, it is of importance to understand the mechanism of HIF-1 degradation after its induction in ischemic brain. This review provides a present understanding of the mechanism of HIF-1 induction in ischemic neurons and the potential effect of HIF-1 on ischemic brain tissue. The author also elaborates on potential therapeutic approaches through understanding of the induction mechanism and of the potential role of HIF-1 in ischemic stroke.
在中风研究中，一个重要的焦点是开发预防神经元死亡和改善恢复的治疗策略。然而，很少有成功的治疗策略出现。缺氧诱导因子 1（HIF-1）是缺氧的关键调节剂。由于其下游基因的功能，它被认为是缺血性中风后神经学结果的重要参与者。这些基因包括促进葡萄糖代谢、血管生成、红细胞生成和细胞存活的基因。许多证据表明，HIF-1 在缺血性大脑中被诱导。重要的是，似乎 HIF-1 主要在缺血性大脑的可挽救组织（半影区）中被诱导。然而，根据体外和临床前研究的证据，HIF-1 对神经元组织损伤的影响仍存在争议。此外，了解缺血性大脑中 HIF-1 诱导后的降解机制也很重要。本综述提供了对缺血性神经元中 HIF-1 诱导机制的现有理解，以及 HIF-1 对缺血性脑组织的潜在影响。作者还通过了解 HIF-1 在缺血性中风中的诱导机制和潜在作用，阐述了潜在的治疗方法。
