Brain research bulletin
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Brain research bulletin · Apr 2010
Plasticity changes of neuronal activities in central lateral nucleus by stimulation of the anterior cingulate cortex in rat.
The medial thalamus (MT) and anterior cingulate cortex (ACC) are essential components in mediating the affective emotional-aspect of pain. Whether ACC modulates the neuron activity in MT has not been elucidated and clarifying this point will further reveal the neurobiological mechanism underlying pain related emotions. ⋯ Tetanic stimulation in the ACC increased spike activities of nociceptive-responding neurons in the CL; retrograde tracing by fluorogold in the CL showed the positive neurons are distributed bilaterally in the ACC. Taken together, we demonstrated descending modulation to nociceptive responses of CL neurons by direct projections from the ACC, which may underlie the neuronal mechanism of negative pain emotions.
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Brain research bulletin · Mar 2010
Comparative StudyComparative biochemical and pharmacological characterization of a novel, NOP receptor selective hexapeptide, Ac-RYYRIR-ol.
Nociceptin/orphanin FQ (N/OFQ) is an endogenous neuropeptide, which is widely distributed in central and peripheral nervous system. Some N/OFQ sequence unrelated hexapeptides can effectively bind to the N/OFQ peptide (NOP) receptor and they were used as template for structure-activity studies that lead to discovery of the new NOP selective ligands. In the present study, the pharmacological profile of the novel hexapeptide Ac-RYYRIR-ol was investigated using various in vitro assays including receptor binding and G-protein activation in rat brain membranes, mouse and rat vas deferens, guinea pig ileum, mouse colon and Ca(2+) mobilization assay in chinese hamster ovary (CHO) cells co-expressing the human recombinant NOP receptor and the C-terminally modified Galpha(qi5) protein. ⋯ In the mouse colon Ac-RYYRIR-ol produced concentration dependent contractile effects with similar potency and maximal effects as N/OFQ. Finally, in the Ca(2+) mobilization assay performed with CHO-hNOP-Galpha(qi5) cells Ac-RYYRIR-ol displayed lower potency and maximal effects (alpha=0.87) compared with N/OFQ. In conclusion, the novel NOP receptor selective hexapeptide Ac-RYYRIR-ol has been shown to have fine selectivity, high potency, furthermore agonist and antagonist effects toward the NOP receptors were measured in various assays; this is likely due to its partial agonist pharmacological activity.
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Brain research bulletin · Mar 2010
LetterResveratrol is neuroprotective because it is not a direct activator of Sirt1-A hypothesis.
The plant polyphenol resveratrol (3,5,4'-trihydroxystilbene) has been touted to have multiple health benefits. A commonly cited mechanism of resveratrol action is via the activation of the longevity factor Sir2/Sirt1, whose deacetylase activity on several transcription factors has stress resistance and pro-survival effects. Resveratrol has been shown to be beneficial in various in vitro and in vivo models of central nervous system (CNS) neuron death and degeneration, presumably acting through Sirt1. ⋯ Furthermore, resveratrol may indirectly increase Sirt1 activity in recovering or spared cells via AMPK's elevation of NAD levels, which then translates into an overall beneficial outcome. The hypothesis could potentially be tested via selective AMPK silencing in various neuronal death and degeneration models, to see if the neuroprotective effect of resveratrol will be blunted. If proven true, the hypothesis has important ramifications in how reseveratrol, as well as novel Sirt1 activators, may be best used in treatment of CNS injuries and disorders.
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Brain research bulletin · Jan 2010
Novel approach to demonstrate high efficacy of mu opioids in the rat vas deferens: a simple model of predictive value.
14-O-Methyloxymorphone and 14-methoxymetopon were reported as highly selective and potent micro opioid receptor agonists. The aim of this study was to demonstrate the opioid activity of these compounds in vitro and in vivo in comparison to oxymorphone, morphine and DAMGO. The micro opioid receptor efficacy, full or partial agonist nature of opioids was analyzed in the rat vas deferens (RVD) bioassay. ⋯ Both, 14-O-methyloxymorphone and 14-methoxymetopon are highly efficacious micro opioid receptor agonists in the RVD exhibiting full micro agonist properties. The RVD tissue contains mu receptors indicated by the comparable K(e) values of the micro antagonist naltrexone against DAMGO in the MVD. RVD may be a good alternative to assess the mu receptor efficacy of opioid agonists providing a more physiological environment for the ligand-receptor interaction than other efficacy measuring methods such as the [(35)S]GTPgammaS binding assay.
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Brain research bulletin · Jan 2010
Prognostic value of biochemical markers of brain damage and oxidative stress in post-surgical aneurysmal subarachnoid hemorrhage patients.
The aim of this study is to determine effective biochemical markers and optimal sampling timing for prediction of neurological prognosis in post-surgical aneurysmal subarachnoid hemorrhage (SAH) patients. Subjects were a sequential group of SAH patients admitted to our centre who underwent aneurysm clipping before Day 3 and who received a cerebrospinal fluid (CSF) drain. CSF samples from 32 patients were collected on Days 3, 7, and 14. ⋯ The area under the receiver-operating characteristic (ROC) curve for MDA on Day 14 was 0.841. For a threshold of 0.3 microM, sensitivity and specificity were 0.875 and 0.750, respectively. Our findings suggest that these biochemical markers, especially MDA, show significant promise as predictors of neurological outcome in clinical practice.