Journal of neurochemistry
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Journal of neurochemistry · Mar 2004
Early anti-inflammatory treatment reduces lipid peroxidation and protein nitration after spinal cord injury in rats.
We investigated mechanisms by which a monoclonal antibody (mAb) against the CD11d subunit of the leukocyte integrin CD11d/CD18 improves neurological recovery after spinal cord injury (SCI) in the rat. The effects of an anti-CD11d mAb treatment were assessed on ED-1 expression (estimating macrophage infiltration), myeloperoxidase activity (MPO, approximating neutrophil infiltration), lipid peroxidation, inducible nitric oxide synthase (iNOS) and nitrotyrosine (indicating protein nitration) expression in the spinal cord lesion after severe clip-compression injury. Protein expression was evaluated by western blotting and immunocytochemistry. ⋯ The mAb treatment also attenuated the expression of iNOS and formation of nitrotyrosine at 6-72 h after SCI. These data indicate that anti-CD11d mAb treatment blocks intraspinal neutrophil and macrophage infiltration, reducing the intraspinal concentrations of reactive oxygen and nitrogen species. These effects likely underlie improved tissue preservation and neurological function resulting from the mAb treatment.
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Journal of neurochemistry · Mar 2004
Role of extracellular signal-regulated kinase in the ventral tegmental area in the suppression of the morphine-induced rewarding effect in mice with sciatic nerve ligation.
We recently reported that micro-opioid receptor agonist morphine failed to induce its rewarding effects in rodents with sciatic nerve injury. In the present study, we investigated whether a state of neuropathic pain induced by sciatic nerve ligation could change the activities of the extracellular signal-regulated kinase (ERK) and p38 in the mouse lower midbrain area including the ventral tegmental area (VTA), and these changes could directly affect the development of the morphine-induced rewarding effect in mice. The sciatic nerve ligation caused a long-lasting and profound thermal hyperalgesia. ⋯ In contrast, i.c.v. treatment with a specific inhibitor of p38, SB203580, did not interfere with the morphine-induced rewarding effect. Immunohistochemical study showed a drastic reduction in phosphorylated-ERK immunoreactivity within tyrosine hydroxylase-positive cells of the VTA. These results suggest that a sustained reduction in the ERK-dependent signalling pathway in dopamine cells of the VTA may be implicated in the suppression of the morphine-induced rewarding effect under neuropathic pain.
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Journal of neurochemistry · Mar 2004
In vivo modulation of extracellular hippocampal glutamate and GABA levels and limbic seizures by group I and II metabotropic glutamate receptor ligands.
The effects of several metabotropic receptor (mGluR) ligands on baseline hippocampal glutamate and GABA overflow in conscious rats and the modulation of limbic seizure activity by these ligands were investigated. Intrahippocampal mGluR group I agonist perfusion via a microdialysis probe [1 mm (R,S)-3,5-dihydroxyphenylglycine] induced seizures and concomitant augmentations in amino acid dialysate levels. The mGlu1a receptor antagonist LY367385 (1 mm) decreased baseline glutamate but not GABA concentrations, suggesting that mGlu1a receptors, which regulate hippocampal glutamate levels, are tonically activated by endogenous glutamate. ⋯ This may partly explain the increased excitation following systemic LY379268 administration and the lack of complete anticonvulsant protection within our epilepsy model with the mGlu2/3 receptor agonist. Group II selective mGluR receptor blockade with LY341495 (1-10 microm) did not alter the rats' behaviour or hippocampal amino acid levels. These data provide a neurochemical basis for the full anticonvulsant effects of mGlu1a and mGlu5 antagonists and the partial effects observed with mGlu2/3 agonists in vivo.