Brain research
-
Bilobalide, a constituent of Ginkgo biloba, has neuroprotective properties. Its mechanism of action is unknown but it was recently found to interact with neuronal transmission mediated by glutamate, gamma-aminobutyric acid (GABA) and glycine. The goal of this study was to test the interaction of bilobalide with glycine in assays of neuroprotection. ⋯ In this model, glycine release was induced by ischemia, an effect that was strongly reduced by bilobalide. We conclude that bilobalide does not interact with glycine receptors in neurochemical assays but it significantly reduces the release of glycine under ischemic conditions. This effect likely contributes to bilobalide's neuroprotective effects in assays of excitotoxicity and ischemia.
-
Vanilloid receptor 1 (VR1) is a noxious receptor and a novel target for pain therapy. Cochinchinenin B (6-hydroxy-7-methoxy-3-(4'-hydroxybenzyl) chromone; CB) is one of the small-molecular components from the flavonoids of Dragon's Blood, a well-known herbal medicine to treat various types of pain. Using whole-cell patch clamp technique, we found that capsaicin (CAP)-activated currents (ICAP) was inhibited by CB with an IC50 of 0.92 mM in acutely isolated rat dorsal root ganglion (DRG) neurons. ⋯ The bind site was on the extracellular part of the channel since intracellular application of CB did not alter the inhibition effect on ICAP. In addition, CB inhibited CAP-evoked depolarization under current-clamp condition. Our findings indicate that CB may be a candidate in developing new analgesic drugs targeting the VR1 receptor.
-
Comparative Study
Exacerbated mechanical allodynia in rats with depression-like behavior.
Although a clinical connection between pain and depression has long been recognized, how these two conditions interact remains unclear. Here we report that both mechanical allodynia and depression-like behavior were significantly exacerbated after peripheral nerve injury in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats with demonstrable depression-like behavior. ⋯ Moreover, there was a lower plasma melatonin concentration and a lower melatonin receptor expression in the anterior cingular cortex in WKY rats than in Wistar rats. These results suggest that there exists a reciprocal relationship between mechanical allodynia and depression-like behavior and the melatoninergic system in the anterior cingular cortex might play an important role in the interaction between pain and depression.
-
The present study aims to investigate changes of spinal cord AMPA receptor GluR1 and its phosphorylation in inflammatory and neuropathic pain. Complete Freund's adjuvant (CFA) injection into the hind paw produced inflammatory thermal hyperalgesia that was assessed by decreased response latency to radiant heat; spinal nerve ligation (SNL) was used to induce mechanical allodynia that was evaluated with von Frey hairs. ⋯ In contrast, neither GluR1 nor pGluR1 showed any significant change in rats following SNL. These results suggest that phosphorylated GluR1 (pGluR1-Ser845 and pGluR1-Ser831) might play a role in the induction of inflammatory but not neuropathic pain.
-
Hypoxia-inducible transcription factor-1 (HIF-1) is critically involved in adaptive endogenous mechanisms to hypoxic brain injury by transcriptional activation of specific target genes that restore oxygen supply. Exogenously, neuroprotective properties of levetiracetam (LEV) have been suggested in experimental cerebral ischemia and epilepsy. We aimed to elucidate 1) effects of acute hypoxic distress on HIF-1 and vasoactive target genes, and 2) effects of LEV on HIF-1-regulated mechanisms in the brain at early developmental stages. ⋯ Moreover, significant changes of VEGF and NOS mRNA levels did not occur with the exception that hypoxia-induced decreased iNOS levels were not observed in P0 brains. We conclude that acute systemic hypoxia differentially affects expression of HIF-1-regulated vasoactive factors in the newborn mouse brain. Of clinical importance, LEV treatment did not alter crucial HIF-1-regulated neuroprotective mechanisms.