Oxygen/glucose deprivation （OGD） has been widely used as an in vitro model of focal ischemia, where the blood flow is severely reduced and neurons rapidly die. However, adjacent to the focal region is ‘penumbra＇, ...Oxygen/glucose deprivation （OGD） has been widely used as an in vitro model of focal ischemia, where the blood flow is severely reduced and neurons rapidly die. However, adjacent to the focal region is ‘penumbra＇, where residual blood flow remains oxygen and glucose supplies are at low levels. To model this pathological genesis, we developed a partial OGD （pOGD） protocol in a rat brain slice. This model met two requirements： oxygen was partially deprived and glucose was reduced in the perfusion buffer. Therefore we investigated the effect of pOGD on gama-aminobutyric acid （GABAA） receptor-mediated inhibitory postsynaptic currents （IPSCs） in CA1 neurons of a hippocampal slice through whole-cell patch-clamp technique. We found that the amplitude and decay time of IPSCs were increased immediately during pOGD treatment. And the enhancement of IPSCs amplitude resulted from an increase of the synaptic conductance without a significant change in the reversal potential of chloride. These results suggested that the nervous system could increase inhibitory neurotransmission to offset excitation by homeostasis mechanisms during the partial oxygen and glucose attack.展开更多
An improved synthesis of rupintrivir (AG7088) was accomplished using three amino acids (L-glutamic acid, D-4-fluorophenylalanine, and L-valine) as the building blocks. The key fragment ketomethylene dipeptide isostere...An improved synthesis of rupintrivir (AG7088) was accomplished using three amino acids (L-glutamic acid, D-4-fluorophenylalanine, and L-valine) as the building blocks. The key fragment ketomethylene dipeptide isostere was constructed with the valine derivative and phenylpropionic acid derivative, followed by coupling with a lactam derivative and an isoxazole acid chloride to provide AG7088 totally in eight steps.展开更多
文摘Oxygen/glucose deprivation （OGD） has been widely used as an in vitro model of focal ischemia, where the blood flow is severely reduced and neurons rapidly die. However, adjacent to the focal region is ‘penumbra＇, where residual blood flow remains oxygen and glucose supplies are at low levels. To model this pathological genesis, we developed a partial OGD （pOGD） protocol in a rat brain slice. This model met two requirements： oxygen was partially deprived and glucose was reduced in the perfusion buffer. Therefore we investigated the effect of pOGD on gama-aminobutyric acid （GABAA） receptor-mediated inhibitory postsynaptic currents （IPSCs） in CA1 neurons of a hippocampal slice through whole-cell patch-clamp technique. We found that the amplitude and decay time of IPSCs were increased immediately during pOGD treatment. And the enhancement of IPSCs amplitude resulted from an increase of the synaptic conductance without a significant change in the reversal potential of chloride. These results suggested that the nervous system could increase inhibitory neurotransmission to offset excitation by homeostasis mechanisms during the partial oxygen and glucose attack.
基金financial support from the National Natural Science Foundation of China (20872153, 21021063, 20720102040 and81025017)the National Basic Research Program of China grant(2009CB918502)+2 种基金the Chinese Academy of Sciences (XDA01040305)the SILVER project of the European Commission (contract HEALTH-F3-2010-260644)supported by a Chinese Academy of Sciences Visiting Professorship for Senior International Scientists (2010T1S6)
文摘An improved synthesis of rupintrivir (AG7088) was accomplished using three amino acids (L-glutamic acid, D-4-fluorophenylalanine, and L-valine) as the building blocks. The key fragment ketomethylene dipeptide isostere was constructed with the valine derivative and phenylpropionic acid derivative, followed by coupling with a lactam derivative and an isoxazole acid chloride to provide AG7088 totally in eight steps.
