Brain research
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There is a high incidence of cardiac arrest and poorer post-resuscitation outcome in the elderly population. Cardiac arrest and resuscitation results in ischemia/reperfusion injury associated with oxidative stress, leading to post-resuscitation mortality and delayed selective neuronal cell loss. In this study we investigated recovery following cardiac arrest and resuscitation in the aged rat brain. ⋯ The time course of mitochondrial function was established using 3-month old Wistar rats with 12-minute cardiac arrest. In the 24-month old rats, overall survival rate, hippocampal CA1 neuronal counts, HVR, and brain mitochondrial respiratory control ratio were significantly reduced following cardiac arrest and resuscitation compared to the younger rats, and PBN treatment improved outcome. The data suggest that (i) there was increased susceptibility to ischemia/reperfusion in aged rat brain; (ii) HVR was decreased in the aged rats; (iii) brain mitochondrial respiratory function related to coupled oxidation was decreased following cardiac arrest and resuscitation in rats, more so in the aged; and (iv) treatment with an antioxidant, such as PBN, reduced the oxidative damage following cardiac arrest and resuscitation.
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As a non-selective agonist of opioid receptors, morphine can also act on the kappa-opioid receptor (KOR) when activating the mu-opioid receptor (MOR) and delta-opioid receptor (DOR). Although previous findings indicate that KOR plays an important role in morphine analgesia and antinociceptive tolerance, the reasons for the paradoxical functions of KOR in analgesia and anti-analgesia responses are still unclear. The aim of this study was to explore the role of the KOR in morphine analgesia and antinociceptive tolerance. ⋯ No other significant changes in KOR expression were observed in the other regions. Consequently, we propose that the locus ceruleus and spinal cord are likely the dominant CNS regions and the DRG is the main peripheral site in which chronic morphine exerts its effect on KOR. Prolonged morphine administration induces inconsistent changes of KOR in the central and peripheral nervous system.
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Cancer induced bone pain (CIBP) is a major clinical problem. Although opioids remain the principal axis in drug therapies for CIBP, their sustained application is known to induce cellular and molecular adaptations including enhanced neuroimmune reactivity. This is generally characterized by glial activation and proinflammatory cytokine production which frequently results in pharmacological tolerance. ⋯ Results showed that chronic morphine use failed to elicit analgesic tolerance in the rat CIBP model. Moreover, the treatment had no significant influence on the activated spinal glia morphology, cell density and expression of special cytomembrane markers, whereas it significantly down-regulated the local proinflammatory cytokine production at the mRNA and protein level. Collectively, these data suggest that chronic morphine treatment in CIBP is not concomitant with pharmacological tolerance, at least partially because the treatment fails to amplify spinal neuroimmune responses.
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In our everyday lives, we need to process auditory and visual temporal information as efficiently as possible. Although automatic auditory time perception has been widely investigated using an index of the mismatch negativity (MMN), the neural basis of automatic visual time perception has been largely ignored. The present study investigated the automatic processing of auditory and visual time perception employing the cross-modal delayed response oddball paradigm. ⋯ The difference in vMMN amplitude was significant between the attention and inattention condition. Auditory MMN does not appear to be modulated by attention, whereas the visual CRP and the vMMN are modulated by attention. Therefore, the present study provides electrophysiological evidence for the existence of automatic visual time perception and supports an "attentional switch" hypothesis for a modality effect on duration judgments, such that auditory temporal information is processed relatively automatically, whereas visual temporal information processing requires controlled attention.
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Fast glutamatergic and GABAergic transmission in the central nucleus of the inferior colliculus (ICC), a major auditory midbrain structure, is mediated respectively by alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic acid (AMPA) and gamma-aminobutyric acid (GABA)(A) receptors. In this study, we used whole-cell patch clamp recordings in brain slices to investigate the effects of activation of metabotropic glutamate receptors (mGluRs) on synaptic responses mediated by AMPA and GABA(A) receptors in ICC neurons of young rats. Excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) mediated respectively by AMPA and GABA(A) receptors were elicited by stimulation of the lateral lemniscus, the major afferent pathway to the ICC. ⋯ The agonists for groups I and III, (RS)-3,5-dihydroxyphenylglycine (DHPG) and L-SOP, respectively, did not affect AMPA or GABA(A) receptor-mediated responses. The reduction of the synaptic responses by LY379268 was accompanied by a substantial increase in a ratio of the second to the first AMPA receptor-mediated EPSCs and GABA(A) receptor-mediated IPSCs to paired-pulse stimulation. The results suggest that group II mGluRs regulate both fast glutamatergic and GABAergic synaptic transmission in the ICC, probably through a presynaptic mechanism due to reduction of transmitter release.