A Cecal Slurry Mouse Model of Sepsis Leads to Acute Consumption of Vitamin C in the Brain

Abstract

Vitamin C (ascorbate, ASC) is a critical antioxidant in the body with specific roles in the brain. Despite a recent interest in vitamin C therapies for critical care medicine, little is known about vitamin C regulation during acute inflammation and critical illnesses such as sepsis. Using a cecal slurry (CS) model of sepsis in mice, we determined ASC and inflammatory changes in the brain following the initial treatment. ASC levels in the brain were acutely decreased by approximately 10% at 4 and 24 h post CS treatment. Changes were accompanied by a robust increase in liver ASC levels of up to 50%, indicating upregulation of synthesis beginning at 4 h and persisting up to 7 days post CS treatment. Several key cytokines interleukin 6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor alpha (TNFα), and chemokine (C-X-C motif) ligand 1 (CXCL1, KC/Gro) were also significantly elevated in the cortex at 4 h post CS treatment, although these levels returned to normal by 48 h. These data strongly suggest that ASC reserves are directly challenged throughout illness and recovery from sepsis. Given the timescale of this response, decreases in cortical ASC are likely driven by hyper-acute neuroinflammatory processes. However, future studies are required to confirm this relationship and to investigate how this deficiency may subsequently impact neuroinflammation.

Ascorbate deficiency decreases dopamine release in gulo–/– and APP/PSEN1 mice

“…Tissue ASC concentrations were measured by ion‐pair HPLC as described previously (Consoli et al., 2020; Harrison et al., 2008; May, Qu, & Mendiratta, 1998). Briefly, sample extracts were prepared by adding 10 µl extraction buffer (7:2 25% w/v metaphosphoric acid: 100 mM sodium phosphate, 0.05 mM EDTA pH 8.0) per mg of wet tissue, normalizing by weight.…”

Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors

“… 16 , 17 Humans are among the few mammals that cannot synthesize vitamin C endogenously 18 and are at risk for vitamin C depletion during sepsis. 19 , 20 , 21 Both vitamin C and hydrocortisone have been associated with decreases in markers of acute inflammation in patients with sepsis 22 , 23 and could act synergistically to prevent and repair endothelial cell dysfunction. 24 , 25 , 26 The adverse cognitive and psychiatric effects of vitamin C deficiency in humans have been recognized for centuries.…”

Epigenetic remodeling by vitamin C potentiates plasma cell differentiation

“…The outcomes from these studies were ambiguous as to whether or not the ‘mega dose’ VC was effective in treating these diseases ( Nauman et al, 2018 ; Thomas et al, 2021 ; Ngo et al, 2019 ; Magrì et al, 2020 ; Klimant et al, 2018 ; Fowler et al, 2019 ; Marik et al, 2017 ). Nonetheless, oral and intravenous VC supplementation may selectively benefit the population with VC deficiency or insufficiency that may cause inferior outcomes ( Consoli et al, 2020 ; Fisher et al, 2014 ; Wu et al, 2004 ).…”