Biocompatible Iron Sulphide Nanoparticles Against Neuroinflammation for Intracerebral Haemorrhage and Long-term Neurological Functional Recovery

Abstract BackgroundMass effects of haematoma, neuroinflammation, oxidative stress, and neuronal apoptosis are the major causes of poor prognosis of intracerebral haemorrhage (ICH). Our previous study suggests that biocompatible iron sulphide nanoparticles possess peroxidase-like activity and can release hydrogen polysulfanes, which may inhibit brain injury. The purpose of this study was to investigate the neuroprotective efficacy of diallyl disulfide (DADS)-nFeS in mice after ICH and preliminarily illustrate the potential mechanism. MethodsAdult male C57BL/6 mice (n = 176) were injected with bacterial collagenase in the striatum. In the first part, DADS-nFeS at different doses (25, 50, or 100 mg/kg) was intragastrically administered 2 h, 26 h, and 50 h before ICH. In the second and third parts, DADS-nFeS (50 mg/kg) was administered 2 h, 26 h, and 50 h before and after the induction of ICH in the pre-treatment group and post-treatment group, respectively. H&E staining was performed to detect drug toxicity. Haematoma volume measurement, Fluoro-Jade C (F-JC) staining, Nissl staining, immunofluorescence staining, western blotting, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining, malondialdehyde (MDA) and superoxide dismutase (SOD) assays, and neurobehavioural tests were performed. ResultsAll three doses of DADS-nFeS had neuroprotective effects, and 50 mg/kg resulted in the best outcome. DADS-nFeS reduced the haematoma volume and MDA content, inhibited the activation of microglia and astrocytes, progressive neuronal degeneration, and apoptosis, increased SOD activity and neuronal survival, and improved both short-term and long-term neurological functions in perihaematomal areas after ICH. Moreover, DADS-nFeS was associated with the downregulation of Iba-1, GFAP, TNF-α, IL-1β, 4-hydroxynonenal (4-HNE), and Bax/Bcl-2 levels in perihaematomal areas after ICH. Finally, post-treatment with DADS-nFeS had a better effect than pre-treatment with DADS-nFeS. ConclusionsOur study indicated that gavage administration of DADS-nFeS decreased the haematoma volume, suppressed neuroinflammation, oxidative stress, and neuronal apoptosis, and improved short- and long-term neurological functions, which was, at least in part, realized by inhibiting the activation of microglia and astrocytes, enhancing local SOD activity, and decreasing the recruitment of reactive oxygen species. Therefore, DADS-nFeS may serve as a potential therapeutic strategy via the diet against central nervous system diseases.