Brain research
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JM-1232(-) (JM) is a novel isoindoline derivative with sedative and hypnotic activities that are mediated by binding to the benzodiazepine site of the Gamma-aminobutyric acid type A (GABAA) receptor. Although the neuroprotective effects of other GABAA receptor agonists are well known, there is no published report regarding JM. Thus, we examined the effects of JM on neurons exposed to oxygen-glucose deprivation (OGD) using rat hippocampal slice cultures. ⋯ To analyze more immediate effects of JM, we next measured the fluorescence of Oregon Green 488 BAPTA-1 during the OGD and re-oxygenation periods, and evaluated changes in intracellular Ca(2+) in single CA1 pyramidal neurons. JM reduced the elevation of intracellular Ca(2+) concentration during OGD, and this effect was antagonized by flumazenil. These findings indicate that JM suppressed the elevation of intracellular Ca(2+) concentration during OGD through GABAA receptors, but its neuroprotective effects from necrotic changes also involve other unknown mechanisms.
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Clinical Trial
Illusion-related brain activations: a new virtual reality mirror box system for use during functional magnetic resonance imaging.
Extended viewing of movements of one's intact limb in a mirror as well as motor imagery have been shown to decrease pain in persons with phantom limb pain or complex regional pain syndrome and to increase the movement ability in hemiparesis following stroke. In addition, mirrored movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain. However, using a so-called mirror box has technical limitations, some of which can be overcome by virtual reality applications. ⋯ In both conditions, subjects reported similar intensities for the sensation that movements of the virtual left hand felt as if they were executed by their own left hand. We found activation in the primary sensorimotor cortex contralateral to the actual movement, with stronger activation for the virtual reality 'mirror box' compared to the classical mirror box condition, as well as activation in the primary sensorimotor cortex contralateral to the mirrored/virtual movement. We conclude that a virtual reality application of the mirror box is viable and that it might be useful for future research.
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Repeated corticosterone (CORT) treatment induces a deficit in dentate gyrus subgranular zone reelin-positive cells, in maturation of newborn neurons, and results in a consistent depressive-like behavior. However, the molecular mechanisms underlying these processes are not known in detail. ⋯ There is a main effect of CORT in the density of both reelin+ and nNOS+ cells in the dentate subgranular zone and hilus, and in reelin+ cells in the molecular layer and CA3 stratum radiatum; and a main effect of genotype on the co-localization of both markers in the dentate subgranular zone, and in the density of reelin+ cell sin the stratum lacunosum moleculare. These alterations suggest a possible interconnection between reelin and nNOS expression that is altered by repeated CORT treatment.
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Early brain injury (EBI) following subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes. Hence, effective therapeutic strategies targeting on EBI have recently become a major goal in the treatment of SAH patients. Baicalein is a flavonoid that has been shown to offer neuroprotection in kinds of brain injury models. ⋯ Baicalein also significantly reduced neural cell death, BBB permeability. These changes were associated with the remarkable reductions of TLR4 expression, IκB-α degradation, NF-κB translocation to nucleus, as well as the expressions of matrix metalloproteinase-9, tight junctions protein, interleukin-1β and tumor necrosis factor- ɑ. These findings suggest that baicalein may ameliorate EBI after SAH potentially via inhibition of inflammation-related pathway.
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Interactions of opioid receptors with other receptor families can be made use of to improve analgesia and reduce adverse effects of opioid analgesics. We investigated interactions of the α2-adrenergic receptor (α2AR) with opioid receptors of the mu (MOR) and delta (DOR) types in the spinal dorsal horn in an animal model of neuropathic pain induced by spinal nerve ligation. Nine days after nerve injury, immunoreactivity for the α2AR subtype A (α2AAR) was increased both in tissue homogenates and at pre- and post-synaptic sites in transverse sections. ⋯ Such an effect was dramatically enhanced by co-administration of a low dose of guanfacine, which reversed thermal and mechanical thresholds to levels near those prior to injury. The results suggest that spinal, α2AAR-mediated antinociception is increased after nerve injury and based on DOR co-activation. We demonstrate in vivo that α2AAR/DOR interaction can be exploited to provide effective behavioral antinociception during neuropathic pain.