ABSTRACT
The delta-opioid receptor (DOR) is one of three classic opioid receptors in the opioid system. It was traditionally thought to be primarily involved in modulating the transmission of messages along pain signaling pathway. Although there were scattered studies on its other neural functions, inconsistent results and contradicting conclusions were found in past literatures, especially in terms of DOR's role in a hypoxic/ischemic brain. Taking inspiration from the finding that the turtle brain exhibits a higher DOR density and greater tolerance to hypoxic/ischemic insult than the mammalian brain, we clarified DOR's specific role in the brain against hypoxic/ischemic injury and reconciled previous controversies in this aspect. Our serial studies have strongly demonstrated that DOR is a unique neuroprotector against hypoxic/ischemic injury in the brain, which has been well confirmed in current research. Moreover, mechanistic studies have shown that during acute phases of hypoxic/ischemic stress, DOR protects the neurons mainly by the stabilization of ionic homeostasis, inhibition of excitatory transmitter release, and attenuation of disrupted neuronal transmission. During prolonged hypoxia/ischemia, however, DOR neuroprotection involves a variety of signaling pathways. More recently, our data suggest that DOR may display its neuroprotective role via the BDNF-TrkB pathway. This review concisely summarizes the progress in this field.
Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Hypoxia-Ischemia, Brain/metabolism , Neuroprotection , Receptor, trkB/metabolism , Receptors, Opioid, delta/metabolism , Signal Transduction , Animals , Brain/metabolism , Brain/pathology , Brain-Derived Neurotrophic Factor/analysis , Humans , Hypoxia-Ischemia, Brain/pathology , Receptor, trkB/analysis , Receptors, Opioid, delta/analysisABSTRACT
The efforts were focused on exploring alternative pneumococcal vaccine strategies, aimed at addressing the shortcomings of existing formulations, without compromising efficacy. We generated a stable Escherichia coli construct expressing functional recombinant PsaA and prepared CPS-rPsaA conjugate. The distribution of anti-CPS antibody response was almost completely of IgG2a subclass followed by IgG3 and low level of IgG1 subclass, which was opposite to the distribution of anti-PsaA IgG subclass antibodies. Though rPsaA was not detectable on the surface of the pneumococcal strain, the CPS-rPsaA conjugate possessed more accessibility to the surface of the strain. Mice immunized with conjugate exhibited rapid bacterial clearance from blood for the first 23h and afterward provided the best protection against challenge with pneumococcal 23F strain.
