Effect of a Nurr1 ligand amodiaquine on pathology of intracerebral hemorrhage in mice
Intracerebral hemorrhage (ICH) is characterized by high mortality and neurological deficits caused by the formation of hematoma in the brain parenchyma. Nurr1 is an orphan nuclear receptor involved in the suppression of pro-inflammatory responses of microglia and astrocytes as well as the maintenance of survival of midbrain dopaminergic neurons. Here we addressed whether Nurr1 serves as a target for ICH therapy, using an anti-malarial drug amodiaquine (AQ) that has been reported to possess agonistic activity on Nurr1. ICH was induced in the striatum of male ICR mice by injection of type VII collagenase. AQ (40 mg/kg) was administered intraperitoneally at 3 h after ICH, and thereafter, every 24 h. Nurr1 expression was observed in microglia in the peri-hematoma region, but not in the contralateral hemisphere. ICH was accompanied by activation of microglia/macrophages and astrocytes in the peri-hematoma region, and also by increased expression of mRNAs encoding inflammatory mediators such as IL-1band CXCL2. These inflammatory responses were markedly attenuated by AQ. Moreover, AQ improved motor function of mice after ICH. These results indicate that Nurr1 activation alleviates pathogenic events associated with ICH.