Neurochemical research
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Neurochemical research · Mar 2015
Tetramethylpyrazine analogue CXC195 ameliorates cerebral ischemia-reperfusion injury by regulating endothelial nitric oxide synthase phosphorylation via PI3K/Akt signaling.
A novel tetramethylpyrazine derivative, CXC195, has been recently shown to protect against cerebral ischemia-reperfusion (I/R) injury. However, the detailed mechanisms underlying the neuroprotection of CXC195 are still unclear. The aim of the present study was to investigate the effects of CXC195 on the phosphorylation of endothelial nitric oxide synthase (eNOS) in response to cerebral I/R and to determine whether phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway might be involved. ⋯ Consistently, CXC195 treatment significantly restored the phosphorylations of eNOS and Akt in the cortical penumbra of rats subjected to 2 h MCAO followed by reperfusion. Moreover, wortmannin abolished CXC195-induced eNOS phosphorylation and neuroprotection as evidenced by a reversal of the reduction in infarct volume and neurobehavioral outcomes. In conclusion, CXC195 induced phosphorylation of eNOS by activation of PI3K/Akt signaling under pathological cerebral I/R conditions, which provided a novel explanation for the neuroprotective effect of CXC195.
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Neurochemical research · Mar 2015
Convergent nociceptive input to spinal dorsal horn neurons after peripheral nerve injury.
The number of c-Fos protein-like immunoreactive (c-Fos-IR) neurons in the spinal dorsal horn evoked by noxious stimulation was previously shown to be increased following peripheral nerve injury, and this increase was proposed to reflect the neuropathic pain state. The aim of this study was to investigate whether anomalous convergent primary afferent input to spinal dorsal horn neurons contributed to nerve injury-induced c-Fos hyperinducibility. Double immunofluorescence labeling for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed to detect convergent synaptic input from different branches of the sciatic nerve after injury to the tibial nerve. c-Fos expression and the phosphorylation of ERK were induced by noxious heat stimulation of the hindpaw and also by electrical stimulation (ES) of the injured tibial nerve, respectively. ⋯ The topographic distribution pattern and number of such p-ERK-IR neurons remained unchanged after the nerve injury. The time course of changes in the number of double-labeled neurons, that presumably received convergent primary afferent input, showed a pattern similar to that of c-Fos-IR neurons after the injury. These results indicate that convergent primary nociceptive input through neighboring intact nerves may contribute to c-Fos hyperinducibility in the spinal dorsal horn.
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Neurochemical research · Mar 2015
Suppression of microRNA-155 attenuates neuropathic pain by regulating SOCS1 signalling pathway.
Chronic neuropathic pain is an unfavourable pathological pain characterised by allodynia and hyperalgesia which has brought considerable trouble to people's physical and mental health, but effective therapeutics are still lacking. MicroRNAs (miRNAs) have been widely studied in the development of neuropathic pain and neuronal inflammation. Among various miRNAs, miR-155 has been widely studied. ⋯ Furthermore, knockdown of SOCS1 abrogated the inhibitory effects of miR-155 inhibition on neuropathic development and neuronal inflammation. Finally, we demonstrated that inhibition of miR-155 resulted in the suppression of nuclear factor-κB and p38 mitogen-activated protein kinase activation by mediating SOCS1. Our data demonstrate the critical role of miR-155 in regulating neuropathic pain through SOCS1, and suggest that miR-155 may be an important and potential target in preventing neuropathic pain development.
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Neurochemical research · Nov 2014
The role of SRC kinase in the caspase-1 pathway after hypoxia in the brain of newborn piglets.
Hypoxia induces a cerebral inflammatory response, which contributes to brain injury. Inflammasomes are complex intracellular molecular structures that initiate the inflammatory cascade. Caspase-1 and interleukin 1-β (IL-1β), have been established as markers of inflammasome activation. ⋯ We provide evidence that inhibition of Src kinase in the acute phase after hypoxia involves changes in the production or processing of caspase-1 subunits. Our data suggest that Src kinase mediates hypoxia-induced caspase-1 activation in the cerebral cortex of newborn piglets. Inhibition of Src kinase may attenuate the neuroinflammatory response and could represent a potential target for neuroprotection after hypoxic injury.
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Neurochemical research · Nov 2014
Progesterone attenuates aquaporin-4 expression in an astrocyte model of ischemia/reperfusion.
Previous studies have suggested that progesterone may be involved in neuroprotection by preventing brain edema. In this study, we assessed the effects of progesterone on aquaporin-4 (AQP4) expression in an ischemia/reperfusion model of cultured rat astrocytes, and further explored the possible role of the protein kinase C (PKC) pathway in this course. We evaluate primary culture astrocytes exposed to 4 h oxygen-glucose deprivation (OGD) followed by 24 h reperfusion (OGD4h/R24h) as a means of simulating cortex ischemia and reperfusion, and test the effect of progesterone on AQP4 expression in response to OGD4h/R24h. ⋯ At a concentration of 1 and 2 μM, progesterone significantly attenuated AQP4 at the level of both protein and mRNA and ameliorated the cell viability of astrocytes from OGD/reperfusion injury. Moreover, this effect was blocked by the PKC inhibitor Ro31-8220, which was employed before the OGD. These results indicate that progesterone exerts the protective effects and attenuates AQP4 expression in an astrocyte model of ischemia/reperfusion depending on the PKC signal pathway.