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- Ajmone-Cat, Maria Antonietta, et al.
(författare)
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Prostaglandin E(2) and BDNF levels in rat hippocampus are negatively correlated with status epilepticus severity: No impact on survival of seizure-generated neurons.
- 2006
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 23:1, s. 23-35
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Tidskriftsartikel (refereegranskat)abstract
- Partial and generalized status epilepticus (pSE and gSE) trigger the same level of progenitor cell proliferation in adult dentate gyrus, but survival of new neurons is poor after gSE. Here, we show markedly elevated levels of prostaglandin E-2 (PGE(2)) and brain-derived neurotrophic factor (BDNF) in rat hippocampal formation at 7 days following pSE but not gSE. Administration of the cyclooxygenase (COX) inhibitor flurbiprofen for 1 week, starting at day 8 post-SE, abated PGE(2) and decreased BDNF levels, but did not affect survival of new neurons a weeks later. Thus, high PGE(2) and BDNF levels induced by pSE are probably not of major importance for survival of new neurons during the first days after formation. We propose that they modulate other aspects of synaptic and cellular plasticity, and thereby may influence epileptogenesis.
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| 2. |
- Ali, Idrish, et al.
(författare)
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Role of fractalkine-CX3CR1 pathway in seizure-induced microglial activation, neurodegeneration, and neuroblast production in the adult rat brain.
- 2015
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 74, s. 194-203
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Tidskriftsartikel (refereegranskat)abstract
- Temporal lobe seizures lead to an acute inflammatory response in the brain primarily characterized by activation of parenchymal microglial cells. Simultaneously, degeneration of pyramidal cells and interneurons is evident together with a seizure-induced increase in the production of new neurons within the dentate gyrus of the hippocampus. We have previously shown a negative correlation between the acute seizure-induced inflammation and the survival of newborn hippocampal neurons. Here, we aimed to evaluate the role of the fractalkine-CX3CR1 pathway for these acute events. Fractalkine is a chemokine expressed by both neurons and glia, while its receptor, CX3CR1 is primarily expressed on microglia. Electrically-induced partial status epilepticus (SE) was induced in adult rats through stereotaxically implanted electrodes in the hippocampus. Recombinant rat fractalkine or CX3CR1 antibody was infused intraventricularly during one week post-SE. A significant increase in the expression of CX3CR1, but not fractalkine, was observed in the dentate gyrus at one week. CX3CR1 antibody treatment resulted in a reduction in microglial activation, neurodegeneration, as well as neuroblast production. In contrast, fractalkine treatment had only minor effects. This study provides evidence for a role of the fractalkine-CX3CR1 signaling pathway in seizure-induced microglial activation and suggests that neuroblast production following seizures may partly occur as a result of microglial activation.
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| 5. |
- Månsson, Roland, et al.
(författare)
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Re-evaluation of mitochondrial permeability transition as a primary neuroprotective target of minocycline.
- 2007
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 25, s. 198-205
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Tidskriftsartikel (refereegranskat)abstract
- Minocycline has been shown to be neuroprotective in ischemic and neurodegenerative disease models and could potentially be relevant for clinical use. We revisited the hypothesis that minocycline acts through direct inhibition of calcium-induced mitochondrial permeability transition (mPT) resulting in reduced release of cytochrome c (cyt c). Minocycline, at high dosage, was found to prevent calcium-induced mitochondrial swelling under energized conditions similarly to the mPT inhibitor cyclosporin A (CsA) in rodent mitochondria derived from the CNS. In contrast to CsA, minocycline dose-dependently reduced mitochondrial calcium retention capacity (CRC) and respiratory control ratios and was ineffective in the de-energized mPT assay. Further, minocycline did not inhibit calcium- or tBid-induced cyt c release. We conclude that the neuroprotective mechanism of minocycline is likely not related to direct inhibition of mPT and propose that the mitochondrial effects of minocycline may contribute to toxicity rather than tissue protection at high dosing in animals and humans.
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