Neuroprotctive effects of CNS-specific prostacyclin receptro ligands

前列环素（PGI 2）是心血管系统的重要调节因子。我们以前的研究表明，PGI 2受体的一种新的亚型，这是明显不同于外周亚型的配体特异性，是在大脑的喙部区域表达。CNS特异性PGI 2受体配体阻止神经元死亡。它们可防止氧化应激诱导的海马神经元凋亡。有效浓度与CNS特异性PGI 2受体的结合效力密切相关。它们还促进培养的隔胆碱能神经元的神经元存活。在体内，15 R-TIC保护沙鼠海马CA 1区锥体神经元免受缺血性损伤，并预防小鼠局灶性缺血引起的神经元损伤。在PET研究中，我们发现外周注射的15 R-TIC在脑的喙部区域积聚。这些结果表明，CNS特异性PGI 2配体在体外和体内均具有神经元存活促进活性，并可能代表一种新型的神经退行性疾病治疗药物。

Prostacyclin (PGI2) is a critical regulator of the cardiovascular system. Our previous studies demonstrated that a novel subtype of PGI2 receptor, which is clearly distinct from a peripheral subtype in terms of ligand specificity, is expressed in the rostral region of the brain. CNS-specific PGI2 receptor ligands prevented the neuronal death. They prevented apoptotic cell death of hippocampal neurons induced oxidative stress. The effective concentrations well correlated with the binding potency for the CNS-specific PGI2 receptor. They also promoted neuronal survival of septal cholinergic neurons in culture. In vivo, 15R-TIC protected CA1 pyramidal neurons against ischemic damage in gerbils and prevented neuronal injury induced by focal ischemia in mice. During the PET study, we found that peripherally-injedted 15R-TIC accumulated in the in the rostral region of the brain. These results indicate that CNS-specific PGI2 ligands have neuronal survival-promoting activity both in vitro and in vivo, and may represent a new type of therapeutic drug for neurodegeneration.