Brain research
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Several recent studies suggest that sumo-2/3 modification of proteins occurs following harmful ischemia, however, sumo-2/3-ylation may also be associated with hibernation-mediated neuroprotection. Here we investigate the sumoylation of proteins following ischemia and ischemic tolerance using our established in vitro model of ischemia (oxygen and glucose deprivation; OGD). Following harmful ischemia (120 min OGD), we observed a significant increase in the sumo-2/3-ylation of high molecular weight proteins (>85 kDa), but not sumo-1-ylation of proteins. ⋯ In addition, we observed a reduction in sumo-2/3-ylation using hypothermia (4 degrees C 30 min) as the preconditioning stimuli to induce delayed ischemic tolerance. Further studies show that sumo-2/3-ylation occurs during the ischemic insult and that preconditioning does not change expression of the sumo E1- and E2-ligases (UBA2 and Ubc9) or the sumo specific isopeptidases (SenP1-3). While sumo-2/3-ylation is enhanced under conditions of cell stress, it is not yet clear whether this is a cause or consequence of harmful ischemia-induced cell damage.
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Neural correlates of conscious awareness can be comfortably studied when awareness of the target stimuli is a varying dependent variable in the experimental conditions where the key independent variables are kept invariant. We presented vernier targets backward masked by an invariant grating with invariant SOA. ⋯ Comparison of data from correct aware trials with data from correct unaware trials showed that conscious awareness of targets was associated with decrease in the latency of ERP/P1, increase in the amplitude of P300, and increase in the power of 70-Hz and 30-Hz gamma band oscillations from 50 ms before target onset up to 100 ms after target onset. Results are interpreted in the context of the well-known views about the role of brain-activity oscillations in conscious awareness and as related to the perceptual retouch theory.
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The mas-related genes (Mrgs, also known as sensory neuron-specific receptors, SNSRs) are specifically expressed in small diameter sensory neurons in the trigeminal and dorsal root ganglia, suggesting an important role of the receptors in pain transmission. The present study aimed to investigate the underlying mechanism of the nociceptive effects after activation of MrgC, and the interaction between MrgC and N/OFQ-NOP receptor system in modulation of nociception in mice. Intrathecal (i.t.) administration of [Tyr(6)] gamma2-MSH(6-12), the most potent agonist for MrgC receptor, produced a significant hyperalgesic response as assayed by tail withdrawal test and a series of characteristic nociceptive responses, including biting, licking and scratching, in a dose-dependent manner (0.01-10 pmol and 0.01-10 nmol, respectively) in mice. ⋯ N/OFQ inhibited nociceptive responses at high doses (0.01-1 nmol), but potentiated the behaviors at low doses (1 fmol-3 pmol). Furthermore, both hyperalgesia and nociceptive responses were enhanced after the co-administration with NOP receptor antagonist [Nphe(1)]N/OFQ(1-13)-NH(2). These results suggest that intrathecal [Tyr(6)] gamma2-MSH(6-12)-induced pronociceptive effects may be mediated through NMDA receptor-NO system in the spinal cord, and demonstrate the interaction between MrgC and N/OFQ-NOP receptor system in pain transmission.
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Recent studies demonstrated that sulfonylurea receptor 1 (SUR 1) regulated nonselective cation channel, the NC(Ca-ATP) channel, is involved in brain injury in rodent models of stroke. Block of SUR 1 with sulfonylurea such as glibenclamide has been shown to be highly effective in reducing cerebral edema, infarct volume and mortality in adult rat models of ischemic stroke. In this study, we tested glibenclamide in both severe and moderate models of neonatal hypoxia-ischemia (HI) in postnatal day 10 Sprague-Dawley rat pups. ⋯ In the severe HI model, glibenclamide, administered immediately after HI and on postoperative Day 1, was not effective in attenuating short-term effects (brain edema and infarct volume) or long-term effects (brain weight and neurological function) of neonatal HI. In the moderate HI model, when injected immediately after HI and on postoperative Day 1, glibenclamide at 0.01 mg/kg improved several neurological parameters at 3 weeks after HI. We conclude that glibenclamide provided some long-term neuroprotective effect after neonatal HI.
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There has been an increasing appreciation of the role that microglial cells play in neural damage. Marrow stromal cells (MSCs) can dramatically lessen neural damage in animal models, but the mechanisms involved have not been defined. This study aimed to investigate the effects of human MSCs (hMSCs) on the activation of primary microglia and the attendant production of pro-inflammatory factors stimulated by bacterial endotoxin lipopolysaccharide (LPS). ⋯ We conclude that hMSCs can inhibit microglial activation and the production of attendant inflammatory factors. In addition, hMSCs can interact with microglial cells through diffusible soluble factors, whereas cell contact is not a prerequisite for anti-inflammatory effects. Finally, hMSCs within inflammatory environment can significantly increase the production of neurotrophic factors, which may involve with the anti-inflammatory mechanisms.