Rilmenidine attenuates intracerebral hemorrhage by regulating autophagy flux and apoptosis via the HO-1/Fe2+/ERK pathway.

Intracerebral hemorrhage (ICH) associated with high mortality and disability rates. The limited understanding of the pathological mechanism of ICH has greatly limited the available treatment options. Rilmenidine (RIL) is a safe and effective imidazoline-1 receptor agonist that has been confirmed by the FDA to have good blood pressure-reducing effects. Moreover, RIL has been shown to be an effective neuroprotective treatment. However, no reports to date have investigated the impact of RIL on ICH.In this study, RIL treatment improved neurobehavioral outcomesand reduced the apoptosis of peripheral neurons surrounding hematomain ICH rats. Here, we showed that hemeoxygenase-1 (HO-1) was highly expressed after ICH, promoted heme degradation, generated Fe2+, activated ERK phosphorylation, and impeded lysosomal degradation to hamper autophagy flux. Immunofluorescence (IF) staining revealed that most of the autophagosomes in the surrounding tissue were confined to axons. Inhibition of HO-1 with RIL alleviated the defects in autophagy. In addition, excessive autophagosome accumulation could activate apoptosis. RIL may play an antiapoptotic role by promoting autophagic degradation, promoting neuronal survival and restoring neural function. The results of this study provide a deeper understanding of the dynamic process of autophagy after ICH, and help to further reveal the mechanism secondary injury in ICH and to develop new therapeutic targets.