المؤلفون: Moretti, Raffaella, Leger, Pierre-Louis, Besson, Valérie, C., Csaba, Zsolt, Pansiot, Julien, Di Criscio, Lorena, Gentili, Andrea, Titomanlio, Luigi, Bonnin, Philippe, Baud, Olivier, Charriaut-Marlangue, Christiane

المساهمون: Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinica Pediatrica – Ospedale di Udine, Università degli Studi di Udine - University of Udine Italie, CHU Trousseau APHP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pharmacologie de la circulation cérébrale (EA 4475), Université Paris Descartes - Paris 5 (UPD5), AP-HP, Hôpital Robert Debré, Pôle de Pédiatrie Aiguë et Médecine Interne, Service d'Accueil des Urgences Pédiatriques, Université Paris Diderot - Paris 7 (UPD7), Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie Clinique, Explorations-Fonctionnelles, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal APHP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Réanimation et Pédiatrie Néonatales, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), INSERM

المصدر: ISSN: 1742-2094 ; Journal of Neuroinflammation ; https://inserm.hal.science/inserm-01316302Test ; Journal of Neuroinflammation, 2016, ⟨10.1186/s12974-016-0560-4⟩.

مصطلحات موضوعية: Neonatal mice, Focal ischemia, Microglia, M2 microglia, Microcirculation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology

الوصف: International audience ; Background: Perinatal ischemic stroke is the most frequent form of cerebral infarction in neonates; however, evidence-based treatments are currently lacking. We have previously demonstrated a beneficial effect of sildenafil citrate, a PDE-5 inhibitor, on stroke lesion size in neonatal rat pups. The present study investigated the effects of sildenafil in a neonatal mouse stroke model on (1) hemodynamic changes and (2) regulation of astrocyte/microglia-mediated neuroinflammation. Methods: Ischemia was induced in C57Bl/6 mice on postnatal (P) day 9 by permanent middle cerebral artery occlusion (pMCAo), and followed by either PBS or sildenafil intraperitoneal (i.p.) injections. Blood flow (BF) velocities were measured by ultrasound imaging with sequential Doppler recordings and laser speckle contrast imaging. Animals were euthanized, and brain tissues were obtained at 72 h or 8 days after pMCAo. Expression of M1-and M2-like microglia/macrophage markers were analyzed. Results: Although sildenafil (10 mg/kg) treatment potently increased cGMP concentrations, it did not influence early collateral recruitment nor did it reduce mean infarct volumes 72 h after pMCAo. Nevertheless, it provided a significant dose-dependent reduction of mean lesion extent 8 days after pMCAo. Suggesting a mechanism involving modulation of the inflammatory response, sildenafil significantly decreased microglial density at 72 h and 8 days after pMCAo. Gene expression profiles indicated that sildenafil treatment also modulates M1-(ptgs2, CD32 and CD86) and M2-like (CD206, Arg-1 and Lgals3) microglia/macrophages in the late phase after pMCAo. Accordingly, the number of COX-2 + microglia/macrophages significantly increased in the penumbra at 72 h after pMCAo but was significantly decreased 8 days after ischemia in sildenafil-treated animals. Conclusions: Our findings argue that anti-inflammatory effects of sildenafil may provide protection against lesion extension in the late phase after pMCAo in neonatal mice. We propose ...

العلاقة: inserm-01316302; https://inserm.hal.science/inserm-01316302Test; https://inserm.hal.science/inserm-01316302/documentTest; https://inserm.hal.science/inserm-01316302/file/Moretti%20et%20al-2016.pdfTest

الإتاحة: https://doi.org/10.1186/s12974-016-0560-4Test
https://inserm.hal.science/inserm-01316302Test
https://inserm.hal.science/inserm-01316302/documentTest
https://inserm.hal.science/inserm-01316302/file/Moretti%20et%20al-2016.pdfTest

المؤلفون: Leger, Pierre-Louis, Pansiot, Julien, Besson, Valérie, C., Palmier, Bruno, Renolleau, Sylvain, Baud, Olivier, Cauli, Bruno, Charriaut-Marlangue, Christiane

المساهمون: Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau APHP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pharmacologie de la circulation cérébrale (EA 4475), Université Paris Descartes - Paris 5 (UPD5), Service Réanimation et surveillance continue médicochirurgicales AP-HP Hôpital Necker-Enfants Malades, Université Paris Descartes - Paris 5 (UPD5)-Hôpital Necker - Enfants Malades AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

المصدر: ISSN: 0039-2499.

مصطلحات موضوعية: COX-2, ischemia–reperfusion, microcirculation, prostaglandins, stroke, [SDV]Life Sciences [q-bio]

الوصف: International audience ; BACKGROUND AND PURPOSE:We previously showed that the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) increases cerebral microcirculation in a juvenile ischemic rat model. We address the roles of cyclooxygenase (COX)-elaborated prostaglandins in collateral recruitment and blood supply.METHODS:Fourteen-day-old rats were subjected to ischemia-reperfusion and treated with either PBS or 7-NI (25 mg/kg) at the reperfusion onset. Six-keto-prostaglandin F1α was measured using ELISA. COX-1 and COX-2 and prostaglandin terminal synthesizing enzymes were evaluated using reverse-transcriptase polymerase chain reaction and immunofluorescence. Microvascular blood flow indexes (artery diameter and capillaries number) were measured using sidestream dark-field videomicroscopy in PBS- and 7-NI-treated ischemic rats in the absence or presence of the COX-2 inhibitor NS-398 (5 mg/kg). Cell death was measured with the TUNEL (terminal transferase dUTP nick end labeling) assay and cleaved-caspase-3 immunostaining.RESULTS:Six-keto-prostaglandin F1α and COX-2, associated with a prostaglandin E synthase, were significantly increased in PBS- and 7-NI-treated animals 15 minutes and 1 hour after ischemia-reperfusion, respectively. In contrast and as compared with PBS, 7-NI significantly decreased prostacyclin synthase and cytosolic prostaglandins E synthase mRNA. Selective COX-2 inhibition significantly decreased blood flow indexes and significantly reversed the effects of 7-NI, including the number of TUNEL+- and cleaved-caspase-3+-nuclei.CONCLUSIONS:These results show that the juvenile rat brains mostly respond to ischemia by a COX-2-dependent prostaglandins production and suggest that the transcriptional responses observed under 7-NI facilitate and reorient COX-2-dependent prostaglandins production.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/27834752; inserm-01415571; https://inserm.hal.science/inserm-01415571Test; https://inserm.hal.science/inserm-01415571/documentTest; https://inserm.hal.science/inserm-01415571/file/Stroke%20PLL-2016.pdfTest; PUBMED: 27834752

الإتاحة: https://doi.org/10.1161/STROKEAHA.116.015095Test
https://inserm.hal.science/inserm-01415571Test
https://inserm.hal.science/inserm-01415571/documentTest
https://inserm.hal.science/inserm-01415571/file/Stroke%20PLL-2016.pdfTest