Neurochemistry international
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Comparative Study
Temporal profile of Src, SSeCKS, and angiogenic factors after focal cerebral ischemia: correlations with angiogenesis and cerebral edema.
A better understanding of the underlying mechanisms of angiogenesis and vascular permeability is necessary for the development of therapeutic strategies for ischemic injury. The purpose of this study was to examine the spatial and temporal expression of Src and Src-suppressed C kinase substrate (SSeCKS) in brain after middle cerebral artery occlusion (MCAO) and elucidate the relationships among Src, SSeCKS, and the key angiogenic factors present after stroke. Rats were subjected to either MCAO or sham operation. ⋯ However, SSeCKS had the reverse correlations. Changes in the expression of these factors correlated with the progress of angiogenesis and cerebral edema. Dynamic temporal changes in Src and SSeCKS expression may modulate angiogenesis and cerebral edema formation after focal cerebral ischemia.
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Comparative Study
Src signaling involvement in Japanese encephalitis virus-induced cytokine production in microglia.
Numerous studies have demonstrated that the disease pathogenesis of Japanese encephalitis involves cytokine-mediated bystander damage. The mechanisms involved in the regulation of Japanese encephalitis virus (JEV)-induced cytokine expression are not well defined but rely mainly on the tight regulation of transcription factor NF-κB. The Src-family tyrosine kinases participate in diversity of cellular signaling and have been demonstrated in JEV-infected cells. ⋯ Pharmacological studies revealed that the integrity of lipid raft and the activation of Src, Ras, Raf, ERK, and NF-κB all contributed to JEV-induced TNF-α and IL-1β expression. Pharmacological and biochemical studies further suggested that Src, upon activation, might transmit signals to the Raf/ERK cascades via Ras-dependent and -independent mechanisms that in turn might lead to NF-κB activation. Overall, our results show that the lipid raft might play a role in mediating JEV-initiated Src/Ras/Raf/ERK/NF-κB signaling and TNF-α/IL-1β expression in microglia.
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The glycosaminoglycan chondroitin sulfate (CS) is a major constituent of the extracellular matrix of the central nervous system where it can constitute part of the perineuronal nets. Constituents of the perineuronal nets are gaining interest because they have modulatory actions on their neighbouring neurons. In this study we have investigated if CS could afford protection in an acute in vitro ischemia/reoxygenation model by using isolated hippocampal slices subjected to 60min oxygen and glucose deprivation (OGD) followed by 120min reoxygenation (OGD/Reox). ⋯ Furthermore, OGD/Reox-induced translocation of p65 to the nucleus was prevented in CS treated hippocampal slices. Finally, CS inhibited iNOS induction caused by OGD/Reox and thereby nitric oxide (NO) production measured as a reduction in DAF-2 DA fluorescence. In conclusion, the protective effect of CS in hippocampal slices subjected to OGD/Reox can be related to a modulatory action of the local immune response by a mechanism that implies inhibition of p38, NFκB, iNOS and the production of NO.
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Comparative Study
Effect of lappaconitine on neuropathic pain mediated by P2X3 receptor in rat dorsal root ganglion.
ATP facilitates initiation and transmission of the neuropathic pain at the dorsal root ganglion (DRG) level via the P2X receptors, especially the subtype P2X(3). Lappaconitine (LA) is an active principle isolated from Chinese herbal medicine and possesses analgesic effect. The aim of this study was to investigate the effect of LA on chronic constriction injury (CCI)-induced neuropathic pain mediated by P2X(3) receptor in the DRG neurons. ⋯ Furthermore, the effect of LA on the P2X(3) receptor agonists ATP- and α,β-meATP-induced inward currents (I(ATP) and I(α,β-meATP)) in the acutely dissociated rat DRG neurons was investigated by whole cell patch-clamp. The results included: (1) There showed reduction of pain thresholds, enhancement of I(ATP) and I(α,β-meATP) and up-regulation of P2X(3) receptor expression in rat DRG neurons when neuropathic pain occurred. (2) In the presence of LA, the decreased pain thresholds, the up-regulated P2X(3) receptor expression and the enhanced I(ATP) and I(α,β-meATP) were reversible in the CCI rats. (3) The down-regulated P2X(3) receptor expression with pretreatment of P2X(3) receptor antisense oligonucleotide significantly attenuated the analgesic effect of LA. These results indicate that the analgesic effect of LA involves decrease of expression and sensitization of the P2X(3) receptors of the rat DRG neurons following CCI.
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Comparative Study
Effects of dexmedetomidine on the release of glial cell line-derived neurotrophic factor from rat astrocyte cells.
Dexmedetomidine (DEX) has been found to improve neuronal survival after transient global or focal cerebral ischemia in rats. Astrocyte cells may possess beneficial properties that promote neuronal recovery by secreting neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF). The purpose of this study was to investigate the effects of DEX on GDNF release from astrocytes and the possible mechanisms involved. ⋯ In addition, the membrane translocation of PKCα was enhanced following DEX treatment. Furthermore, we found that DEX stimulated GDNF release rescued neurons against OGD-induced neurotoxicity; this effect was partly abolished by GDNF antibody. Thus, through α2A adrenergic receptors, DEX may activate astrocytes, and promote GDNF release to protect neurons after stroke, and this signaling is possibly dependent on PKCα and CREB activation.