Neurochemical research
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Neurochemical research · Aug 2009
Activation of NMDA receptor is associated with up-regulation of COX-2 expression in the spinal dorsal horn during nociceptive inputs in rats.
Cyclooxygenases-2 (COX-2) in the spinal dorsal horn is up-regulated and plays an important role in pain and hyperalgesia induced by nociceptive stimulation. The mechanisms involved in the up-regulation of spinal COX-2 during nociceptive stimulation are yet not well understood. Because the important role of NMDA and its receptor in transmission of nociceptive information in the spinal cord, activation of the spinal NMDA receptor might contribute to the up-regulation of spinal COX-2 expression. ⋯ Whereas, intrathecal injection of NMDA significantly up-regulated the expression of COX-2 in the spinal dorsal horn in a time course corresponding to that of nociceptive behavioral responses elicited by the intrathecal NMDA administration. In addition, the up-regulation of the COX-2 expression induced by the intrathecal NMDA was dose-dependent and blocked by prior administration of MK-801. These findings proved that activation of NMDA receptor is associated with the up-regulation of COX-2 expression in the spinal dorsal horn during nociceptive stimulation in rats.
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Neurochemical research · Jul 2009
Case ReportsSepsis associated encephalopathy studied by MRI and cerebral spinal fluid S100B measurement.
The pathogenesis of sepsis associated encephalopathy (SAE) is not yet clear: the blood-brain barrier (BBB) disruption has been indicated among the possible causative mechanisms. S100B, a calcium binding protein, originates in the central nervous system but it can be also produced by extra-cerebral sources; it is passively released from damaged glial cells and neurons; it has limited passage through the BBB. We aimed to demonstrate BBB damage as part of the pathogenesis of SAE by cerebral spinal fluid (CSF) and serum S100B measurements and by magnetic resonance imaging (MRI). ⋯ S100B does not increase in CSF of septic patients; S100B increase in serum may be due to extracerebral sources and does not prove any injury of BBB. MRI can exclude other cerebral pathologies causing brain dysfunction but is not specific of SAE. BBB damage may be numbered among the contributors of SAE, which aetiology is certainly multifactorial: an interplay between the toxic mediators involved in sepsis and the indirect effects of hyperthermia, hypossia and hypoperfusion.
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Neurochemical research · Jun 2009
Delayed treatment with carboxy-PTIO permits a 4-h therapeutic window of opportunity and prevents against ischemia-induced energy depletion following permanent focal cerebral ischemia in mice.
We examined whether a nitric oxide scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-L: -oxyl-3-oxide (carboxy-PTIO), could offer neuroprotective actions and improve cerebral energy metabolism in a model of stroke. Sixty C57BL/10J mice were given either carboxy-PTIO (0.3-1.2 mg/kg) or vehicle intraperitoneally, 0.5 h after permanent middle cerebral artery occlusion, to evaluate the dose-response effects. An additional 70 animals received carboxy-PTIO (0.6 mg/kg) or vehicle, 2-6 h post-ischemia, for establishing the therapeutic window. ⋯ Four hour post-ischemia, ATP depleted in the ischemic hemisphere (P < 0.05). Administration with carboxy-PTIO not only improved the recovery of ATP in the ischemic hemisphere (P < 0.05), but also enhanced adenosine content across the ischemic and non-ischemic hemispheres (P < 0.05). The neuroprotection of carboxy-PTIO may be partly attributed to the beneficial effects of improving cerebral energy metabolism.
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Neurochemical research · Jun 2009
ReviewZebrafish Rohon-Beard neuron development: cdk5 in the midst.
Cyclin-dependent kinase 5 (cdk5) is a proline-directed serine/threonine kinase that is activated mostly by association with its activators, p35 and p39. Initially projected as a neuron-specific kinase, cdk5 is expressed ubiquitously and its kinase activity solely depends on the presence of its activators, which are also found in some non-neuronal tissues. As a multifunctional protein, cdk5 has been linked to axonogenesis, cell migration, exocytosis, neuronal differentiation and apoptosis. ⋯ One of the functions that we have followed for the cdk5 ortholog in zebrafish in vivo is its effect on the Rohon-Beard (RB) neurons. RB neurons are the primary sensory spinal neurons that die during the first two days of zebrafish development eventually to be replaced by the dorsal root ganglia (DRG). Based on ours studies and others', here we discuss possible mechanisms that may be involved in cdk5's role in RB neuron development and survival.
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Gliomas are the most common tumours of the central nervous system (CNS) and a frequent cause of mental impairment and death. Treatment of malignant gliomas is often palliative because of their infiltrating nature and high recurrence. Genetic events that lead to brain tumours are mostly unknown. ⋯ In addition, the possible role of Platelet Derived Growth Factor receptor type alpha (PDGFR-alpha) and Notch signalling in normal development and tumourigenesis of gliomas are also discussed. Future work elucidating the mechanisms that control normal development will help to identify new cancer stem cell-related genes. The identification of important markers and the elucidation of signalling pathways involved in survival, proliferation and differentiation of CSCs appear to be fundamental for developing an effective therapy of brain tumours.