Fasudil attenuates lipopolysaccharide-induced cognitive impairment in C57BL/6 mice through anti-oxidative and anti-inflammatory effects: Possible role of aquaporin-4

Abstract

Introduction

Processes that generate systemic inflammation are strongly associated with neurodegenerative diseases. This study aimed to explore the potential anti-oxidative and anti-inflammatory effects of fasudil and its role in modulating aquaporin-4 (AQP-4) to improve cognitive impairment in a systemic inflammation model induced by lipopolysaccharide (LPS).

Method

fourty C57BL/6 mice were assigned to four groups, including sham, LPS, sham+fasudil, and LPS+fasudil). Intraperitoneal LPS was given (500 μg/kg/day) at hours 0, 24, 48, and 72, and fasudil (30 mg/kg) administered intraperitoneal injections 2 hours after LPS injection. The open field, Y-maze, and Novel object tasks was used to assess learning and memory. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the hippocampus also measured as markers of oxidative stress and inflammation. Furthermore, the expression of AQP-4 measured in the intact and experimental groups.

Results

The results showed that Fasudil significantly improved memory and anxiety behavior induced by LPS in the open field maze, spatial recognition memory in the Y-maze, and performance in the novel object recognition task. It also mitigates hippocampal MDA and SOD levels. Additionally, fasudil ameliorated LPS-induced hippocampal levels of TNFα and IL-10 and increased hippocampal levels of AQP-4 expression in mice.

Conclusion

Our results suggest that fasudil in the LPS model of systemic inflammation could improve cognition by suppressing oxidative stress and inflammation and increasing AQP-4 protein expression. These findings highlighted the potential of fasudil as a neuroprotective agent. However, further research is required to fully understand its neuroprotective properties in the treatment of neurodegenerative disorders.