Background: Recent studies suggest that the novel neuropeptide orexin-A may play an essential role during neuronal damage. However, the function of orexin-A during brain ischemia remains unclear. Recently, hypoxia-inducible factor-1␣ (HIF-1␣) was shown to be activated by orexin-A. The aim of the current study is to test the hypothesis that administration of exogenous orexin-A can attenuate ischemia-reperfusion injury through the facilitation of HIF-1␣ expression. Methods: Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 120 min. Rats were treated with different doses of orexin-A or vehicle before the ischemia and at the onset of reperfusion. To investigate the action of HIF-1␣ in the neuroprotective effects of orexin-A, the HIF-1␣ inhibitor YC-1 was used alone or combined with orexin-A. Neurologic deficit scores and infarct volume were assessed. Brains were harvested for immunohistochemical staining and western blot analysis. Results: Orexin-A significantly ameliorated neurologic deficit scores and reduced infarct volume after cerebral ischemia reperfusion. Administration of 30 g/kg orexin-A showed optimal neuroprotective effects. This effect was still present 7 days after reperfusion. Furthermore, orexin-A decreased the number of apoptotic cells and significantly enhanced HIF-1␣
Inhibition of ubiquitin-conjugated protein aggregation may have an essential role in inducing cerebral ischemic tolerance by isoflurane preconditioning in a transient global cerebral ischemia-reperfusion injury mouse model.
Radial migration is an important process in the evolution of the Galactic disk. The metallicity gradient of open clusters and its outliers provide an effective way to examine this process. In this work, we compile metallicity, age, and kinematic parameters for 225 open clusters and carry out a quantitative analysis of radial migration via the calculated migration distances. Based on clusters with age <0.5 Gyr, we obtain a present-day metallicity gradient of −0.074 ± 0.007 dex kpc−1. Three sequences are distributed along this gradient, and clusters in the upper, middle, and lower groups are found to be old outward migrators, in situ clusters, and inward migrators, respectively. The migration distance increases with age, but the time when it is most effective is probably less than 3 Gyr. The metallicity gradient breaks at guiding center radius R
g
∼ 11.5 kpc, which is caused by the lack of young open clusters in the outer disk and the presence of old outward migrators in the upper sequence. This shows that this boundary is related to the different effects of radial migration between the inner and outer disks. We also found many special open clusters in and near the outer disk with R > 11 kpc and a steeper metallicity gradient from the inner disk of R
g
< 7 kpc, which tells of a complicated evolution history of the Galactic disk caused by different effects of stellar radial migration.
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