Neuropharmacology
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Exposure to the group I metabotropic glutamate receptor (mGluR) agonist dihydroxyphenylglycine (DHPG) produces long-lasting changes in network excitability and epileptiform activity in the CA3 region of rat hippocampal slices that continues in the absence of the agonist and includes both interictal and more prolonged ictal-like activity. We evaluated the afterhyperpolarization (AHP) that follows repetitive neuronal firing in neurons exposed to DHPG and related the change in the AHP to the pattern of epileptiform activity. In contrast to neurons from control slices that had a robust AHP following neuronal depolarization and action potential generation, neurons that had been exposed to DHPG displayed a minimal AHP following depolarization. ⋯ Co-application of either 1-EBIO or DCEBIO with DHPG blocked the induction of epileptiform activity. Transient DHPG exposure caused a long-term suppression of the AHP and ictal patterns of epileptiform activity. 1-EBIO or DCEBIO which re-established both the medium and slow AHP suppressed ictal discharges. These results support the hypothesis that the loss of the AHP contributes to the generation of ictal activity after transient DHPG exposure.
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Icariin (ICA) has neuroprotection in oxygen-glucose deprivation (OGD) neurons by increasing Sirtuin1 (SIRT1). However, little is known about the role of ICA on stroke. SIRT1 is a class III histone deacetylase and activates peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) which stimulates mitochondrial activity. ⋯ Expressions of SIRT1 and PGC-1alpha were also investigated. In result, neurological scores, infarct size and brain edema were all significantly improved, the cortical expressions of SIRT1 and PGC-1alpha were higher with ICA compared to the control (P < 0.05), and reversed by SIRT1 inhibitor III/PGC-1alpha siRNA. In conclusion, ICA protects against brain ischemic injury by increasing the SIRT1 and PGC-1alpha expression, potentially to be a neuroprotectant for ischemic brain injury.