Cellular and molecular neurobiology
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Cell. Mol. Neurobiol. · Nov 2008
Local loperamide inhibits thermal hyperalgesia but not mechanical allodynia induced by intratibial inoculation of melanoma cells in mice.
The stimulation of peripheral opioid receptors counteracts thermal hyperalgesia produced by the intratibial inoculation of NCTC 2472 cells in mice, through the activation of the nitric oxide/cGMP/ATP-sensitive K+-channels (NO/cGMP/K(+) (ATP)) cascade (Menéndez et al. 2007, Neuropharmacology 53:71-80). We aimed to elucidate whether this peripheral opioid antihyperalgesic effect is exclusive to this model or might also occur in other types of bone neoplastic processes. In C57BL/6 mice intratibially inoculated with B16-F10 melanoma cells, the progressive tumoral damage was accompanied by the establishment of thermal hyperalgesia (unilateral hot plate test) and mechanical allodynia (von Frey test). ⋯ The fact that the coadministration of naloxone-methiodide (5 microg) completely suppressed the thermal antihyperalgesic effect induced by loperamide indicates its production through the stimulation of peripheral opioid receptors. Furthermore, its prevention by the coadministration of the non-selective inhibitor of the NO synthase, N(G)-monomethyl-L-arginine (L-NMMA, 10 microg), the selective inhibitor of neural NOS, N-omega-propyl-L-arginine (1-10 microg), or the K+ (ATP) channel blocker, glibenclamide (10 microg) demonstrated the involvement of the NO/cGMP/K(+) (ATP) pathway in the antihyperalgesic effect induced by loperamide. Overall, the present results show that the intratibial inoculation of B16-F10 cells to C57BL/6 mice evokes thermal hyperalgesia and mechanical allodynia and that, as occurred in the osteosarcoma model, the stimulation of peripheral opioid receptors is not effective in modifying neoplastic allodynia but completely inhibits thermal hyperalgesia through the activation of the NO/cGMP/K+ (ATP) cascade.
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Cell. Mol. Neurobiol. · Aug 2008
The neuroprotective potential of phase II enzyme inducer on motor neuron survival in traumatic spinal cord injury in vitro.
(1) Phase II enzyme inducer is a kind of compound which can promote the expression of antioxidative enzymes through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Recently, it has been reported that these compounds show neuroprotective effect via combating oxidative stress. The purpose of this study is to determine whether phase II enzyme inducers have neuroprotective effects on traumatic spinal cord injury. (2) An organotypic spinal cord culture system was used, Phase II enzyme inducers were added to culture medium for 1 week, motor neurons were counted by SMI-32 staining, glutamate, Nrf2, and Heme oxygenase-1(HO-1) mRNA were tested. (3) This study showed motor neuron loss within 1 week in culture. ⋯ Necrotic motor neuron and damaged mitochondrial were observed in culture 48 h. Furthermore, phase II enzyme inducers: tert-butyhydroquinone (t-BHQ), 3H-1,2-dithiole-3-thione (D3T), and 5,6-dihydrocyclopenta-1,2-dithiole-3-thione (CPDT) were shown to promote motor neuron survival after dissection, it was due to increasing Nrf2 and HO-1 mRNA expression and protecting mitochondrial not due to decreasing glutamate level. (4) The loss of motor neuron due to dissection can mimic severe traumatic spinal cord injury. These results demonstrate that glutamate excitotoxicity and the damage of mitochondrial is possibly involve in motor neuron death after traumatic spinal cord injury and phase II enzyme inducers show neuroprotective potential on motor neuron survival in traumatic spinal cord injury in vitro.
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Cell. Mol. Neurobiol. · Jun 2008
Neuroprotective mechanism of taurine due to up-regulating calpastatin and down-regulating calpain and caspase-3 during focal cerebral ischemia.
Taurine as an endogenous substance possesses a number of cytoprotective properties. In the study, we have evaluated the neuroprotective effect of taurine and investigated whether taurine exerted neuroprotection through affecting calpain/calpastatin or caspase-3 actions during focal cerebral ischemia, since calpain and caspase-3 play central roles in ischemic neuronal death. ⋯ Our data demonstrate the dose-dependent neuroprotection of taurine against transient focal cerebral ischemia, and suggest that one of protective mechanisms of taurine against ischemia may be blocking the m-calpain and caspase-3-mediated apoptotic cell death pathways.
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Cell. Mol. Neurobiol. · Feb 2008
The role of TNF-alpha and its receptors in the production of beta-1,4-galactosyltransferase I mRNA by rat primary type-2 astrocytes.
beta-1,4-galactosyltransferase I (beta-1,4-GalT I) plays an important role in the synthesis of the backbone structure of adhesion molecules involved in leukocyte-endothelial cell interaction. The expression of beta-1,4-GalT I mRNA increased in primary human endothelial cells after exposure to tumor necrosis factor-alpha (TNF-alpha). In the central nervous system (CNS), astrocytes play a pivotal role in immunity as immunocompetent cells by secreting cytokines and inflammatory mediators, there are two types of astrocytes. ⋯ From these results, we conclude that TNF-alpha signaling via both TNFR1 and TNFR2 translocated from nucleus to cytoplasm or processes is sufficient to induce beta-1,4-GalT I mRNA. In addition, we observed that not only exogenous TNF-alpha but also TNF-alpha produced by type-2 astrocytes affected beta-1,4-GalT I mRNA production in type-2 astrocytes. These results suggest that an autocrine loop involving TNF-alpha contributes to the production of beta-1,4-GalT I mRNA in response to inflammation.
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Cell. Mol. Neurobiol. · Oct 2006
ReviewBone marrow stem cells and polymer hydrogels--two strategies for spinal cord injury repair.
1. Emerging clinical studies of treating brain and spinal cord injury (SCI) led us to examine the effect of autologous adult stem cell transplantation as well as the use of polymer scaffolds in spinal cord regeneration. We compared an intravenous injection of mesenchymal stem cells (MSCs) or the injection of a freshly prepared mononuclear fraction of bone marrow cells (BMCs) on the treatment of an acute or chronic balloon-induced spinal cord compression lesion in rats. ⋯ Our clinical study suggests a possible positive effect in patients with SCI. Bridging the lesion cavity can be an approach for further improving regeneration. Our preclinical studies showed that macroporous polymer hydrogels based on derivatives of HEMA or HPMA are suitable materials for bridging cavities after SCI; their chemical and physical properties can be modified to a specific use, and 3D implants seeded with different cell types may facilitate the ingrowth of axons.