Time-dependent effects of dexamethasone on glutamate binding, ornithine decarboxylase activity and polyamine levels in the transected spinal cord

González, Susana; Coirini, Héctor; Deniselle, Marı́a Claudia González; Gonzalez, S. I.; Calandra, Ricardo S.; Nicola, Alejandro F. De

doi:10.1016/0960-0760(95)00160-2

Cited by 15 publications

(6 citation statements)

References 38 publications

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“…ODC and putrescine levels significantly increase after SCI [3], [31], [32]. We hypothesize that coordinating these processes and other sequential processes such as spermine expression, enhancement of nitric oxide, and purinergic pathways will be effective to influence innate immune processes after SCI [33].…”

Section: Discussionmentioning

confidence: 94%

Establishment of Quantitative Severity Evaluation Model for Spinal Cord Injury by Metabolomic Fingerprinting

et al. 2014

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Spinal cord injury (SCI) is a devastating event with a limited hope for recovery and represents an enormous public health issue. It is crucial to understand the disturbances in the metabolic network after SCI to identify injury mechanisms and opportunities for treatment intervention. Through plasma 1H-nuclear magnetic resonance (NMR) screening, we identified 15 metabolites that made up an “Eigen-metabolome” capable of distinguishing rats with severe SCI from healthy control rats. Forty enzymes regulated these 15 metabolites in the metabolic network. We also found that 16 metabolites regulated by 130 enzymes in the metabolic network impacted neurobehavioral recovery. Using the Eigen-metabolome, we established a linear discrimination model to cluster rats with severe and mild SCI and control rats into separate groups and identify the interactive relationships between metabolic biomarkers in the global metabolic network. We identified 10 clusters in the global metabolic network and defined them as distinct metabolic disturbance domains of SCI. Metabolic paths such as retinal, glycerophospholipid, arachidonic acid metabolism; NAD–NADPH conversion process, tyrosine metabolism, and cadaverine and putrescine metabolism were included. In summary, we presented a novel interdisciplinary method that integrates metabolomics and global metabolic network analysis to visualize metabolic network disturbances after SCI. Our study demonstrated the systems biological study paradigm that integration of 1H-NMR, metabolomics, and global metabolic network analysis is useful to visualize complex metabolic disturbances after severe SCI. Furthermore, our findings may provide a new quantitative injury severity evaluation model for clinical use.

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Section: Discussionmentioning

confidence: 94%

Establishment of Quantitative Severity Evaluation Model for Spinal Cord Injury by Metabolomic Fingerprinting

et al. 2014

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“…A GR-homodimer binds to nuclear-specific DNA responsive elements and regulates gene transcription and translation for a number of cellular elements (Drouin et al, 1992;Karst et al 2002). In addition, GR action could take place through nongenomic mechanisms (Barrett and Vedeckis, 1996;Refojo et al, 2001), including (1) the GR-mediated inhibition of bradykinin-induced Ca 2ϩ influx in PC12 cells (Qiu et al, 2003), (2) the effect of cortisol through GRs on prolactin release (Borski et al, 2002), (3) regulation by GRs of glutamate binding in the injured spinal cord (Gonzalez et al, 1995), and (4) a corticosterone-induced acute elevation of intracellular Ca 2ϩ concentration in hippocampal neurons (Takahashi et al, 2002). Of interest is that a number of previous studies have suggested that GRs may have modulatory effects on the expression and function of NMDAR.…”

Section: Discussionmentioning

confidence: 99%

Expression of Central Glucocorticoid Receptors after Peripheral Nerve Injury Contributes to Neuropathic Pain Behaviors in Rats

Wang¹,

Lim²,

Zeng³

et al. 2004

J. Neurosci.

114

121

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Peripheral glucocorticoid receptors (GRs) play a significant role in the anti-inflammatory effects of glucocorticoids; however, the role of central GRs in nociceptive behaviors after peripheral nerve injury (neuropathic pain behaviors) remains unknown. Here we show that the development of neuropathic pain behaviors (thermal hyperalgesia and mechanical allodynia) induced by chronic constriction nerve injury (CCI) in rats was attenuated by either the GR antagonist RU38486 (4 ϭ 2 Ͼ 1 ϭ 0.5 g) or a GR antisense oligonucleotide administered intrathecally twice daily for postoperative days 1-6. The development of thermal hyperalgesia and mechanical allodynia after CCI also was prevented in adrenalectomized rats, whereas the GR agonist dexamethasone (100 g/kg) given subcutaneously twice daily for postoperative day 1-6 restored CCI-induced neuropathic pain behaviors in the adrenalectomized rats. Mechanistically, CCI induced a time-dependent and region-specific expression of neuronal GRs primarily within the spinal cord dorsal horn ipsilateral to nerve injury, which showed a time course parallel to that of the development of neuropathic pain behaviors. Moreover, the expression of neuronal GR after CCI was mediated in part through an elevated spinal level of interleukin-6 (IL-6) and protein kinase C␥ (PKC␥), because intrathecal treatment with an IL-6 antiserum, a PKC inhibitor (cheryrithrine), or PKC␥ knock-out substantially reduced the expression of neuronal GRs as well as neuropathic pain behaviors after CCI. These findings indicate a central role of neuronal GRs in the mechanisms of neuropathic pain behaviors in rats and suggest a potential role for GR antagonists in clinical management of neuropathic pain.

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“…For example, (1) interactions between GRs and activating protein-1 or nuclear factor B have been shown to be involved in the process of immunosuppression and anti-inflammation (Barrett and Vedeckis, 1996;Refojo et al, 2001); (2) GRs mediate the inhibition of bradykinin-induced Ca 2ϩ influx in PC12 cells (Qiu et al, 2003); (3) the regulatory role of cortisol in prolactin release is mediated through GRs (Borski et al, 2002); (4) GRs regulate spinal glutamate binding to glutamate receptors after spinal cord injury (Gonzalez et al, 1995); (5) GRs mediate acute elevation of the intracellular Ca 2ϩ concentration induced by corticosterone in hippocampal neurons (Takahashi et al, 2002); and (6) activation of GRs potentiates NMDAR-mediated responses in dopamine-sensitive neurons within the ventral tegmental area (Cho and Little, 1999) as well as long-term depression (Coussens et al, 1997). Collectively, these previous studies strongly indicate that activation of GRs could directly interact with cellular components through nongenomic regulation, thereby modulating cellular events.…”

Section: Discussionmentioning

confidence: 99%

Central Glucocorticoid Receptors Modulate the Expression and Function of Spinal NMDA Receptors after Peripheral Nerve Injury

Wang¹,

Lim²,

Zeng³

et al. 2005

J. Neurosci.

124

116

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Central glucocorticoid receptors (GRs) and NMDA receptors (NMDARs) have been shown to play a significant role in the mechanisms of neuropathic pain after peripheral nerve injury; however, how central GRs and NMDARs interact in this process remains unknown. Here we show that the expression and function of spinal NMDARs after peripheral nerve injury were modulated by central GRs. Chronic constriction nerve injury (CCI) in rats induced a time-dependent upregulation of NR1 and NR2 subunits of the NMDAR within the spinal cord dorsal horn ipsilateral to CCI. The upregulation of NMDARs was significantly diminished by intrathecal administration (twice daily for postoperative days 1-6) of either the GR antagonist RU38486 or an antisense oligonucleotide against GRs. Moreover, this CCI-induced expression of NMDARs was significantly attenuated in rats receiving intrathecal treatment with an interleukin-6 (IL-6) antiserum and in mice with protein kinase C␥ (PKC␥) knock-out. Because IL-6 and PKC␥ mediated the upregulation of central GRs after CCI as demonstrated previously, the results suggest that IL-6 and PKC␥ served as cellular mediators contributing to the GR-mediated expression of NMDARs after CCI. Functionally, nociceptive behaviors induced by NMDAR activation and CCI were reversed by a single intrathecal administration of the GR antagonist RU38486. Conversely, a single intrathecal injection with the noncompetitive NMDAR antagonist MK-801 reversed neuropathic pain behaviors exacerbated by the GR agonist dexamethasone in CCI rats. These data suggest that interactions between central GRs and NMDARs through genomic and nongenomic regulation may be an important mechanism critical to neuropathic pain behaviors in rats.

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Time-dependent effects of dexamethasone on glutamate binding, ornithine decarboxylase activity and polyamine levels in the transected spinal cord

Cited by 15 publications

References 38 publications

Establishment of Quantitative Severity Evaluation Model for Spinal Cord Injury by Metabolomic Fingerprinting

Establishment of Quantitative Severity Evaluation Model for Spinal Cord Injury by Metabolomic Fingerprinting

Expression of Central Glucocorticoid Receptors after Peripheral Nerve Injury Contributes to Neuropathic Pain Behaviors in Rats

Central Glucocorticoid Receptors Modulate the Expression and Function of Spinal NMDA Receptors after Peripheral Nerve Injury

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