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J Pharm Pharmacol ; 72(5): 709-718, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32037551

RESUMEN

OBJECTIVES: Gadolinium (Gd) affects microglial polarization during remyelination. We previously reported that the suppression of proinflammatory microglia was neuroprotective in intracerebral haemorrhage (ICH). The objective of the present study was to investigate the effects of Gd on microglial polarization and neuronal injury after ICH. METHODS: Gadolinium was intraperitoneally administered to ICH mice prepared by an intrastriatal microinjection of collagenase type VII. The polarization of M1, 2a, b and c microglia was evaluated by real-time PCR using the respective markers. Changes in representative mRNAs were also confirmed by immunological methods. Neuroprotective effects were evaluated by counting NeuN-positive cells and a behavioural analysis. KEY FINDINGS: One day after ICH, the mRNA levels of proinflammatory M1 microglial markers, such as inducible nitric oxide synthase (iNOS), and anti-inflammatory M2 microglial markers, such as arginase1 (M2a, c), Ym1 (M2a), and transforming growth factor-ß (M2c), increased, while those of chemokine CCL1 (M2b) only increased after 3 days. Gd decreased the levels of all M1 and M2 markers. Arginase1 and iNOS protein levels also increased, and Gd reduced them due to apoptotic cell death. Gadolinium attenuated oedema, neuron loss, neurological deficits and the mortality rate without affecting haematoma sizes. CONCLUSIONS: Gadolinium induced M1 and M2 microglial apoptosis and exerted acute neuroprotective effects after ICH.


Asunto(s)
Apoptosis/efectos de los fármacos , Hemorragia Cerebral/tratamiento farmacológico , Gadolinio/uso terapéutico , Microglía/efectos de los fármacos , Microglía/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Animales , Arginasa/metabolismo , Conducta Animal/efectos de los fármacos , Biomarcadores/metabolismo , Edema Encefálico/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patología , Quimiocina CCL1/metabolismo , Masculino , Ratones , Fármacos Neuroprotectores/farmacología , Óxido Nítrico Sintasa de Tipo II/metabolismo , ARN Mensajero/metabolismo , Factor de Crecimiento Transformador beta/metabolismo
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