Protective effects and mechanisms of high-dose vitamin C on sepsis-associated cognitive impairment in rats

37Citations
Citations of this article
32Readers
Mendeley users who have this article in their library.

Abstract

Sepsis survivors present long-term cognitive deficits. The present study was to investigate the effect of early administration of high-dose vitamin C on cognitive function in septic rats and explore its possible cerebral protective mechanism. Rat sepsis models were established by cecal ligation and puncture (CLP). Ten days after surgery, the Morris water maze test was performed to evaluate the behavior and cognitive function. Histopathologic changes in the hippocampus were evaluated by nissl staining. The inflammatory cytokines, activities of antioxidant enzymes (superoxide dismutase or SOD) and oxidative products (malondialdehyde or MDA) in the serum and hippocampus were tested 24 h after surgery. The activity of matrix metalloproteinase-9 (MMP-9) and expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) in the hippocampus were measured 24 h after surgery. Compared with the sham group in the Morris water maze test, the escape latency of sepsis rats was significantly (P = 0.001) prolonged in the navigation test, whereas the frequency to cross the platform and the time spent in the target quadrant were significantly (P = 0.003) reduced. High-dose vitamin C significantly decreased the escape latency (P = 0.01), but increased the time spent in the target quadrant (P = 0.04) and the frequency to cross the platform (P = 0.19). In the CLP+ saline group, the pyramidal neurons were reduced and distributed sparsely and disorderly, the levels of inflammatory cytokines of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the serum and hippocampus were significantly increased (P = 0.000), the blood brain barrier (BBB) permeability in the hippocampus was significantly (P = 0.000) increased, the activities of SOD in the serum and hippocampus were significantly (P = 0.000 and P = 0.03, respectively) diminished while the levels of MDA in the serum and hippocampus were significantly (P = 0.007) increased. High-dose vitamin C mitigated hippocampus histopathologic changes, reduced systemic inflammation and neuroinflammation, attenuated BBB disruption, inhibited oxidative stress in brain tissue, and up-regulated the expression of nuclear and total Nrf2 and HO-1. High-dose vitamin C significantly (P < 0.05) decreased the levels of tumor necrosis factor- (TNF)-α, interleukin-6 (IL-6), MDA in the serum and hippocampus, and the activity of MMP-9 in the hippocampus, but significantly (P < 0.05) increased the levels of SOD, the anti-inflammatory cytokine (IL-10) in the serum and hippocampus, and nuclear and total Nrf2, and HO-1 in the hippocampus. In conclusion, high-dose vitamin C can improve cognition impairment in septic rats, and the possible protective mechanism may be related to inhibition of inflammatory factors, alleviation of oxidative stress, and activation of the Nrf2/HO-1 pathway.

References Powered by Scopus

The third international consensus definitions for sepsis and septic shock (sepsis-3)

18479Citations
N/AReaders
Get full text

Morris water maze: Procedures for assessing spatial and related forms of learning and memory

3586Citations
N/AReaders
Get full text

Long-term cognitive impairment and functional disability among survivors of severe sepsis

1898Citations
N/AReaders
Get full text

Cited by Powered by Scopus

The Key Drivers of Brain Injury by Systemic Inflammatory Responses after Sepsis: Microglia and Neuroinflammation

38Citations
N/AReaders
Get full text

Current Understanding of Long-Term Cognitive Impairment After Sepsis

30Citations
N/AReaders
Get full text

Newly synthesized chitosan-nanoparticles attenuate carbendazim hepatorenal toxicity in rats via activation of Nrf2/HO1 signalling pathway

23Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Zhang, N., Zhao, W., Hu, Z. J., Ge, S. M., Huo, Y., Liu, L. X., & Gao, B. L. (2021). Protective effects and mechanisms of high-dose vitamin C on sepsis-associated cognitive impairment in rats. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-93861-x

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 6

60%

Lecturer / Post doc 3

30%

Researcher 1

10%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 5

45%

Neuroscience 2

18%

Agricultural and Biological Sciences 2

18%

Medicine and Dentistry 2

18%

Article Metrics

Tooltip
Social Media
Shares, Likes & Comments: 3

Save time finding and organizing research with Mendeley

Sign up for free