Abstract
BackgroundInflammasomes are involved in diverse inflammatory diseases. Previous study reported that the neurotransmitter dopamine inhibited NLRP3 inflammasome activation via dopamine D1 receptor (DRD1). The present study aims to investigate the role of DRD1 on neuroinflammation in intracerebral hemorrhage (ICH) mice and the potential mechanism mediated by NLRP3 inhibition.MethodsOne hundred and six male CD-1 mice were subjected to intrastriatal injection of bacterial collagenase or PBS. A68930 (DRD1 specific agonist) was administered by subcutaneous injection at 1 h after collagenase injection. Behavioral deficits and brain water content were assayed. The expression of Iba 1 and MPO levels were measured by immunofluorescence staining. The expressions of proteins in the DRD1/interferon-beta (IFN-beta)/NLRP3 signaling pathway were evaluated by western blotting.ResultsActivation of the DRD1 by A68930 decreased brain edema and improved behavior at 24 and 72 h of ICH. A68930 inhibited partly the activation of microglia and the neutrophil infiltration after 24 h of ICH. IFN-beta, p-STAT1 increased while NLRP3, caspase 1, and IL-1beta decreased after A68930 administration in ICH mice. DRD1 antagonist and IFN-beta siRNA reversed effects of A68930 on neurological outcome and brain edema. DRD1 antagonist and IFN-beta siRNA blocked not only A68930-mediated increases of IFN-beta, p-STAT1 but also A68930-mediated decreases of NLRP3, caspase 1, and IL-1beta.ConclusionsDRD1 activation by A68930 improves neurological outcome through inhibition of NLRP3-mediated inflammation in ICH mice.
Highlights
Inflammasomes are involved in diverse inflammatory diseases
In the present study, we demonstrated that activation of Dopamine D1 receptor (DRD1) improved neurological outcome through inhibition of NLRP3-mediated inflammation in intracerebral hemorrhage (ICH) mice
It showed that DRD1 plays a primary role, while Dopamine D2 receptor (DRD2), DRD3, and DRD4 have no roles in dopamine-mediated NLRP3 inflammasome inhibition [11]
Summary
Inflammasomes are involved in diverse inflammatory diseases. Previous study reported that the neurotransmitter dopamine inhibited NLRP3 inflammasome activation via dopamine D1 receptor (DRD1). The present study aims to investigate the role of DRD1 on neuroinflammation in intracerebral hemorrhage (ICH) mice and the potential mechanism mediated by NLRP3 inhibition. Intracerebral hemorrhage (ICH) is a devastating subtype of stroke and accounts for 10–15% of all stroke cases [1]. Inflammation is an important host defense response to brain injury after ICH. When ICH occurs, blood components enter the cerebral parenchyma. The inflammatory response begins immediately after the presence of blood components in the parenchyma, and is characterized by accumulation and activation of inflammatory cells. The resident microglia and astrocytes are believed to be the early inflammatory cells in response to the extravascular
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