Neuroprotective Effects of a PSD-95 Inhibitor in Neonatal Hypoxic-Ischemic Brain Injury.

The postsynaptic density-95 inhibitor NA-1 uncouples NMDA glutamate receptors from downstream neurotoxic signaling pathways without affecting normal glutamate receptor function. NA-1 attenuates NMDA receptor-mediated neuronal cell death after stroke in multiple models and species. However, its efficacy in providing neuroprotection in models of neonatal hypoxic-ischemic brain injury has not yet been tested. In this study, a modified version of the Rice-Vannucci method for the induction of neonatal hypoxic-ischemic brain injury was performed on postnatal day 7 mouse pups. Animals received a single dose of NA-1 intraperitoneally either before or after right common carotid artery occlusion. All experiments were performed in a blinded manner. Infarct volumes were measured 1 and 7 days after the injury, while behavioral tests were conducted 1, 3, and 7 days after injury. Administration of NA-1 before right common carotid artery occlusion or immediately after ischemia significantly reduced infarct volume and improved neurobehavioral outcomes 1, 3, and 7 days post-injury. The neuroprotection and improvement in neurobehavioral outcomes conferred by NA-1 in this mouse neonatal hypoxic-ischemic injury model imply that NA-1 will be effective in reducing neonatal stroke damage and thus could potentially serve as a therapeutic drug for prevention or treatment of neonatal stroke.

Marine compound xyloketal B reduces neonatal hypoxic-ischemic brain injury.

Neonatal hypoxic-ischemic encephalopathy causes neurodegeneration and brain injury, leading to sensorimotor dysfunction. Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508) with unique antioxidant effects. In this study, we investigated the effects and mechanism of xyloketal B on oxygen-glucose deprivation-induced neuronal cell death in mouse primary cortical culture and on hypoxic-ischemic brain injury in neonatal mice in vivo. We found that xyloketal B reduced anoxia-induced neuronal cell death in vitro, as well as infarct volume in neonatal hypoxic-ischemic brain injury model in vivo. Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult. In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury. Our findings indicate that xyloketal B is effective in models of hypoxia-ischemia and thus has potential as a treatment for hypoxic-ischemic brain injury.

[Effect of c-myb on hCG-induced testosterone secretion in isolated rat Leydig cells].

The present study was carried out to investigate the effect of antisense c-myb oligodeoxynucleotides (ODN) on hCG-induced testosterone secretion in isolated rat Leydig cells. The effects of cAMP, Ca(2+) and cycloheximide (CYX) on c-Myb protein expression and testosterone secretion were also observed. The results showed that antisense c-myb ODN inhibited hCG-induced testosterone secretion of isolated rat Leydig cells in a dose-dependent manner. At the same time, integral optical density immunostaining of Myb in Leydig cells was also remarkably reduced. Nonsense tat ODN had no effect on Leydig cells. Further experiments showed that dbcAMP (100 micromol/L) obviously increased hCG-induced testosterone secretion and integral optical density (IOD) immunostaining of Myb in Leydig cells. Verapamil (10 micromol/L), a Ca(2+) channel blocker, and cycloheximide (50 microg/ml), a protein synthesis inhibitor, reduced the immunostaining of c-Myb, and also lowered hCG-induced testosterone secretion in isolated rat Leydig cells. The results indicate that c-myb closely correlates with hCG-induced testosterone secretion, and that cAMP and Ca(2+)-dependent pathway participates in the expression of protooncogene.