Abstract
BackgroundAluminum overload can cause severe brain injury and neurodegeneration. Previous studies suggest that prostacyclin synthase (PGIS) expression and prostacyclin receptor (IP) activation are beneficial for treatment of acute traumatic and ischemic brain injury. However, the potential value of PGIS/IP signaling pathway to chronic brain injury is still unclear. In this study, we investigated the change of PGIS/IP signaling pathway and the effect of beraprost sodium (BPS) on chronic brain injury in chronic aluminum-overload rats.MethodsRat model of chronic cerebral injury was established by chronic intragastric administration of aluminum gluconate(Al3+ 200 mg/kg per day,5d a week for 20 weeks). The methods of ELISA, qRT-PCR and Western blotting were used to detect the PGI2 level and the PGIS and IP mRNA and protein levels in hippocampi of chronic aluminum-overload rats, respectively. Rat hippocampal superoxide dismutase (SOD) activity and malondialdehyde (MDA) content also were measured. The effects of BPS (6, 12 and 24 μg⋅kg-1) on brain injury in chronic aluminum-overload rats were evaluated.ResultsCompared with the control group, PGIS mRNA expression, PGI2 level, and the IP mRNA and protein expressions significantly increased in hippocampi of chronic aluminum-overload rats. Administration of BPS significantly improved spatial learning and memory function impairment and hippocampal neuron injury induced by chronic aluminum overload in rats. Meanwhile, administration of BPS resulted in a decrease of PGI2 level and downregulation of PGIS and IP expressions in a dose-dependent manner. Aluminum overload also caused a decrease of SOD activity and an increase of MDA content. Administration of BPS significantly blunted the decrease of SOD activity and the increase of MDA content induced by aluminum overload in rats.ConclusionsBPS has a significant neuroprotective effect on chronic brain injury induced by aluminum overload in rats. Remodeling the balance of PGIS/IP signaling pathway and inhibition of oxidative stress involve in the neuroprotective mechanism of BPS in aluminum-overload rats. The PGIS/IP signaling pathway is a potential therapeutic strategy for chronic brain injury patients.
Highlights
Aluminum overload can cause severe brain injury and neurodegeneration
Autopsy results of dead rats showed no obvious abnormality in peripheral tissues or organs
The administration of beraprost sodium (BPS) significantly prevented the histopathological changes of hippocampal neurons caused by aluminum overload in rats (Figure 1)
Summary
Aluminum overload can cause severe brain injury and neurodegeneration. Previous studies suggest that prostacyclin synthase (PGIS) expression and prostacyclin receptor (IP) activation are beneficial for treatment of acute traumatic and ischemic brain injury. The potential value of PGIS/IP signaling pathway to chronic brain injury is still unclear. We investigated the change of PGIS/IP signaling pathway and the effect of beraprost sodium (BPS) on chronic brain injury in chronic aluminum-overload rats. The physiological action of aluminum to humans is not clear. It is well known that aluminum overload can cause severe brain injury and neurodegeneration since the aluminum toxicity to humans was first reported at early 1970s. Aluminum could play a role in chronic brain damage and neurodegeneration by enhancing oxidative stress and inflammation [4]. The mechanism of aluminum neurotoxicity is not well understood and should be further clarified
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
