Neuroprotctive effects of CNS-specific prostacyclin receptro ligands

前列环素（PGI2）是心血管系统的关键调节剂。我们之前的研究表明，一种新的PGI2受体亚型，在配体特异性方面明显不同于外周亚型，在大脑的吻侧区域表达。中枢神经系统特异性PGI2受体配体阻止神经元死亡。它们可以防止海马神经元氧化应激引起的凋亡细胞死亡。有效浓度与cns特异性PGI2受体的结合力密切相关。它们还能促进培养的中隔胆碱能神经元的存活。在体内，15R-TIC可保护沙鼠CA1锥体神经元免受缺血性损伤，并可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15R-TIC在大脑吻侧区积累。这些结果表明，cns特异性PGI2配体在体外和体内均具有促进神经元存活的活性，可能是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.