Abstract: Nitric oxide (NO\mathbin{\hbox{\tenbsy\char"01}} ) can lead to damaging or protective actions in the central nervous system. Here we consider the chemistry of the NO group and its redox‐related species that can lead to these exactly opposite ends. In the neurodestructive mode, NO\mathbin{\hbox{\tenbsy\char"01}} reacts with superoxide anion (O_{2}\mathbin{\hbox{\tenbsy\char"01}}^- ) to form peroxynitrite (ONOO^{-} ), which leads to neuronal injury. In contrast, the reaction of the NO group with cysteine sulfhydryls on the NMDA receptor leads to a decrease in receptor/channel activity, avoidance of excessive Ca^{2+} entry, and thus neuroprotection. Site‐directed mutagenesis of recombinant NMDA receptor subunits has recently increased our knowledge…of such redox modulation by NO. Transfer of the NO group to cysteine sulfhydryls on the NMDA receptor or other proteins, known as S‐nitrosylation, is becoming recognized as a ubiquitous regulatory reaction, akin to phosphorylation, and represents a form of redox modulation in diverse tissues including the brain.
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Citation: Biofactors,
vol. 8, no. 1-2, pp. 33-40, 1998
Abstract: Purpose: Acute spinal cord injury (SCI) triggers multiple cellular and molecular pathways; therapy aimed at only one pathway is unlikely to succeed. Anecdotal reports indicate that a novel herbal formulation (JSK—Ji-Sui-Kang) may enhance recovery in humans with SCI. We investigated whether JSK's therapeutic effects could be verified in a well-established SCI model in rats. Methods: Therapeutic effects of JSK were tested using a standard behavioral assessment, histological, immunochemical and microarray analysis. Phytochemical fingerprinting of JSK was performed using high performance liquid chromatography coupled with photodiode array detection and electrospray ionization-mass spectrometry. JSK or vehicle was gavaged to rats 24 hours…after SCI and daily thereafter for 3 weeks. Results: Locomotor function significantly improved (n = 12; p < 0.05), tissue damage was reduced (p < 0.01; n = 6) and more axons and myelin were observed in JSK-treated compared with vehicle control animals. JSK significantly enhanced expression of neuroglobin, vascular endothelial growth factor and growth-associated protein 43, and reduced the expression of caspase 3, cyclooxygenase-2, RhoA (p < 0.05; n = 6) and fibrinogen (p < 0.01; n = 6). RNA microarray indicated that JSK altered transcription of genes involved in ischemic and inflammatory/immune responses and apoptosis (p < 0.05; n = 3). Conclusions: JSK appears to target multiple biochemical and cellular pathways to enhance functional recovery and improve outcomes of SCI. The results provide a basis for further investigation of JSK's effects following SCI.
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