Microglial involvement in neuroplastic changes following focal brain ischemia in rats.
The pathogenesis of ischemic stroke is a complex sequence of events including inflammatory reaction, for which the microglia appears to be a major cellular contributor. However, whether post-ischemic activation of microglial cells has beneficial or detrimental effects remains to be elucidated, in pa...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-12-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19956568/pdf/?tool=EBI |
| _version_ | 1818394642695061504 |
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| author | Alexandre Madinier Nathalie Bertrand Claude Mossiat Anne Prigent-Tessier Alain Beley Christine Marie Philippe Garnier |
| author_facet | Alexandre Madinier Nathalie Bertrand Claude Mossiat Anne Prigent-Tessier Alain Beley Christine Marie Philippe Garnier |
| author_sort | Alexandre Madinier |
| collection | DOAJ |
| description | The pathogenesis of ischemic stroke is a complex sequence of events including inflammatory reaction, for which the microglia appears to be a major cellular contributor. However, whether post-ischemic activation of microglial cells has beneficial or detrimental effects remains to be elucidated, in particular on long term brain plasticity events. The objective of our study was to determine, through modulation of post-stroke inflammatory response, to what extent microglial cells are involved in some specific events of neuronal plasticity, neurite outgrowth and synaptogenesis. Since microglia is a source of neurotrophic factors, the identification of the brain-derived neurophic factor (BDNF) as possible molecular actor involved in these events was also attempted. As a means of down-regulating the microglial response induced by ischemia, 3-aminobenzamide (3-AB, 90 mg/kg, i.p.) was used to inhibit the poly(ADP-ribose) polymerase-1 (PARP-1). Indeed, PARP-1 contributes to the activation of the transcription factor NF-kB, which is essential to the upregulation of proinflammatory genes, in particular responsible for microglial activation/proliferation. Experiments were conducted in rats subjected to photothrombotic ischemia which leads to a strong and early microglial cells activation/proliferation followed by an infiltration of macrophages within the cortical lesion, events evaluated at serial time points up to 1 month post-ictus by immunostaining for OX-42 and ED-1. Our most striking finding was that the decrease in acute microglial activation induced by 3-AB was associated with a long term down-regulation of two neuronal plasticity proteins expression, synaptophysin (marker of synaptogenesis) and GAP-43 (marker of neuritogenesis) as well as to a significant decrease in tissue BDNF production. Thus, our data argue in favour of a supportive role for microglia in brain neuroplasticity stimulation possibly through BDNF production, suggesting that a targeted protection of microglial cells could represent an innovative approach to potentiate post-stroke neuroregeneration. |
| first_indexed | 2024-12-14T06:04:27Z |
| format | Article |
| id | doaj.art-3a4ed85037274a8a8b4d46cedbb14128 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T06:04:27Z |
| publishDate | 2009-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3a4ed85037274a8a8b4d46cedbb141282022-12-21T23:14:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-12-01412e810110.1371/journal.pone.0008101Microglial involvement in neuroplastic changes following focal brain ischemia in rats.Alexandre MadinierNathalie BertrandClaude MossiatAnne Prigent-TessierAlain BeleyChristine MariePhilippe GarnierThe pathogenesis of ischemic stroke is a complex sequence of events including inflammatory reaction, for which the microglia appears to be a major cellular contributor. However, whether post-ischemic activation of microglial cells has beneficial or detrimental effects remains to be elucidated, in particular on long term brain plasticity events. The objective of our study was to determine, through modulation of post-stroke inflammatory response, to what extent microglial cells are involved in some specific events of neuronal plasticity, neurite outgrowth and synaptogenesis. Since microglia is a source of neurotrophic factors, the identification of the brain-derived neurophic factor (BDNF) as possible molecular actor involved in these events was also attempted. As a means of down-regulating the microglial response induced by ischemia, 3-aminobenzamide (3-AB, 90 mg/kg, i.p.) was used to inhibit the poly(ADP-ribose) polymerase-1 (PARP-1). Indeed, PARP-1 contributes to the activation of the transcription factor NF-kB, which is essential to the upregulation of proinflammatory genes, in particular responsible for microglial activation/proliferation. Experiments were conducted in rats subjected to photothrombotic ischemia which leads to a strong and early microglial cells activation/proliferation followed by an infiltration of macrophages within the cortical lesion, events evaluated at serial time points up to 1 month post-ictus by immunostaining for OX-42 and ED-1. Our most striking finding was that the decrease in acute microglial activation induced by 3-AB was associated with a long term down-regulation of two neuronal plasticity proteins expression, synaptophysin (marker of synaptogenesis) and GAP-43 (marker of neuritogenesis) as well as to a significant decrease in tissue BDNF production. Thus, our data argue in favour of a supportive role for microglia in brain neuroplasticity stimulation possibly through BDNF production, suggesting that a targeted protection of microglial cells could represent an innovative approach to potentiate post-stroke neuroregeneration.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19956568/pdf/?tool=EBI |
| spellingShingle | Alexandre Madinier Nathalie Bertrand Claude Mossiat Anne Prigent-Tessier Alain Beley Christine Marie Philippe Garnier Microglial involvement in neuroplastic changes following focal brain ischemia in rats. PLoS ONE |
| title | Microglial involvement in neuroplastic changes following focal brain ischemia in rats. |
| title_full | Microglial involvement in neuroplastic changes following focal brain ischemia in rats. |
| title_fullStr | Microglial involvement in neuroplastic changes following focal brain ischemia in rats. |
| title_full_unstemmed | Microglial involvement in neuroplastic changes following focal brain ischemia in rats. |
| title_short | Microglial involvement in neuroplastic changes following focal brain ischemia in rats. |
| title_sort | microglial involvement in neuroplastic changes following focal brain ischemia in rats |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19956568/pdf/?tool=EBI |
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