Journal: Brain, behavior, and immunity

Article Title: Lipocalin-2 perpetuates postoperative and post-infectious neuroinflammation and anxiety-like behavior

doi: 10.1016/j.bbi.2026.106535

Figure Lengend Snippet: Lipocalin-2 is persistently upregulated in sepsis survivors. (A) Volcano plot and table showing lipocalin-2 as the top upregulated transcript in the hippocampus three weeks after CLP in male and female mice. (B) Lcn2 gene counts are higher in CLP brains compared to SHAM brain. N = 15 SHAM, n = 11 CLP. (C) Lcn2 gene counts are higher in the brains of patients who died of an infection than in the brains of those who died of non-infectious causes. N = 12 per group. (D-F) Circulating LCN2 protein is persistently upregulated in plasma in survivors of CLP (D), cecal slurry (E), and Klebsiella pneumoniae lung infection (F) in male and female mice. N = 19 SHAM, n = 13 CLP; n = 10 VEH, n = 9 CS; n = 3 VEH, n = 6 KP. Bars represent mean ± SEM or median with interquartile range. *p < 0.05, **p < 0.01, ****p < 0.0001 in two-tailed independent t-tests and Mann-Whitney U tests.

Article Snippet: Plasma and serum LCN2 levels were quantified according to the manufacturer’s protocol using a mouse lipocalin-2 ELISA kit (RayBiotech).

Techniques: Infection, Clinical Proteomics, Two Tailed Test, MANN-WHITNEY

Journal: Brain, behavior, and immunity

Article Title: Lipocalin-2 perpetuates postoperative and post-infectious neuroinflammation and anxiety-like behavior

doi: 10.1016/j.bbi.2026.106535

Figure Lengend Snippet: Tamoxifen successfully abrogates LCN2 upregulation in lcn2 loxP -CreER T2 mice. (A) Experimental timeline (n = 8–11 per group, ~50% males). (B) CLP mice have an 81.6% overall survival. (C-H) Treatment of CreER T2+ mice, but not CreER T2− mice (C-E), with tamoxifen prevents the increase in LCN2 levels 17 days after CLP in plasma (F) and liver (G) and decreases them in the brain (H). Bars represent mean ± SEM. P-values represent the results of 2-way ANOVA; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 Tukey’s HSD post-hoc tests following 2-way ANOVA.

Article Snippet: Plasma and serum LCN2 levels were quantified according to the manufacturer’s protocol using a mouse lipocalin-2 ELISA kit (RayBiotech).

Techniques: Clinical Proteomics

Journal: Brain, behavior, and immunity

Article Title: Lipocalin-2 perpetuates postoperative and post-infectious neuroinflammation and anxiety-like behavior

doi: 10.1016/j.bbi.2026.106535

Figure Lengend Snippet: Brain lcn2 RNA levels are positively correlated with other markers of innate immune activation. (A-C) In vehicle and tamoxifen-injected SHAM mice of both genotypes, brain lcn2 levels are positively correlated with brain lrg1 (A), selp (B), and s100a8 (C) RNA levels. (D-F) In vehicle and tamoxifen-injected CLP mice of both genotypes, brain lcn2 levels are also positively correlated with brain lrg1 (D), selp (E), and s100a8 (F) RNA levels. N = 8–11 per group, ~50% males. P-values represent the results of Spearman correlations.

Article Snippet: Plasma and serum LCN2 levels were quantified according to the manufacturer’s protocol using a mouse lipocalin-2 ELISA kit (RayBiotech).

Techniques: Activation Assay, Injection

Journal: Brain, behavior, and immunity

Article Title: Lipocalin-2 perpetuates postoperative and post-infectious neuroinflammation and anxiety-like behavior

doi: 10.1016/j.bbi.2026.106535

Figure Lengend Snippet: A shorter tamoxifen treatment regimen that does not independently influence behavior also decreases lcn2 RNA expression. (A) Experimental timeline (n = 8–15 per group ~ 50% males). (B) CLP mice have a 71.4% overall survival. (C-E) This treatment prevents the increase in LCN2 protein levels in serum (C), lcn2 RNA levels in CLP survivor mice in the liver (D) while minimizing them in the brain (E). Bars represent mean ± SEM. P-values represent the results of log-rank (Mantel-Cox) test and 2-way ANOVA; *p < 0.05, **p < 0.01, ****p < 0.0001 Tukey’s HSD post-hoc tests following 2-way ANOVA.

Article Snippet: Plasma and serum LCN2 levels were quantified according to the manufacturer’s protocol using a mouse lipocalin-2 ELISA kit (RayBiotech).

Techniques: RNA Expression

Journal: Brain, behavior, and immunity

Article Title: Lipocalin-2 perpetuates postoperative and post-infectious neuroinflammation and anxiety-like behavior

doi: 10.1016/j.bbi.2026.106535

Figure Lengend Snippet: LCN2 perpetuates neuroinflammation and behavioral deficits in SHAM and CLP survivor mice. (A-C) At the group level, CLP and lcn2 knockout have minimal effects on locomotion and anxiety-like behaviors in the elevated zero maze. (D-F) Similarly, CLP and lcn2 knockout have minimal effects on locomotion and anxiety-like behaviors in the open field at the group level. (G) Regression estimates show that higher brain lcn2 RNA expression (log2 fold change) is associated with increased anxiety-like behaviors in the elevated zero maze and open field (analysis involving all groups). (H) Regression estimates show that higher brain lcn2 RNA expression (log2 fold change) is associated with increased anxiety-like behaviors in the elevated zero maze and open field (analysis involved CLP groups only). (I-K) In CLP mice of both genotypes, brain lcn2 RNA levels are positively correlated with those of lrg1 (I), selp (J), but not s100a8 (K). Bars represent mean ± SEM. For regression estimates, error bars represent 95% confidence intervals. P-values represent the results of Spearman correlations.

Article Snippet: Plasma and serum LCN2 levels were quantified according to the manufacturer’s protocol using a mouse lipocalin-2 ELISA kit (RayBiotech).

Techniques: Knock-Out, RNA Expression

Journal: Brain, behavior, and immunity

Article Title: Lipocalin-2 perpetuates postoperative and post-infectious neuroinflammation and anxiety-like behavior

doi: 10.1016/j.bbi.2026.106535

Figure Lengend Snippet: Laparotomy induces persistent increases in circulating LCN2 protein and brain lcn2 RNA, as well as anxiety-like behavior. (A) Experimental timeline (n = 16 per treatment group, 50% males). (B) Circulating LCN2 levels remain elevated 20 days after laparotomy. (C-E) Laparotomy does not affect distance traveled, time spent in open areas, or open area entries in the elevated zero maze, although a significant main effect of sex can be observed for all measures. (F-H) Laparotomy reduces total distance traveled and exploration of the center in the open field. (I-L) qPCR analyses show that brain lcn2 , lrg1 , and s100a8 , but not selp , RNA levels are increased 20 days post-laparotomy. (M–O) Correlational analyses reveal that brain lcn2 RNA levels are positively correlated with lrg1 and s100a8 RNA levels, but not selp . Bars represent mean ± SEM. P-values reflect results from two-way ANOVA or Spearman correlations; *p < 0.05, **p < 0.01 in two-tailed independent t-tests and Tukey’s HSD post-hoc tests following 2-way ANOVA.

Article Snippet: Plasma and serum LCN2 levels were quantified according to the manufacturer’s protocol using a mouse lipocalin-2 ELISA kit (RayBiotech).

Techniques: Two Tailed Test

Journal: Brain, behavior, and immunity

Article Title: Lipocalin-2 perpetuates postoperative and post-infectious neuroinflammation and anxiety-like behavior

doi: 10.1016/j.bbi.2026.106535

Figure Lengend Snippet: Longitudinal analysis of calcium activity and neuron registration reveals that acute rLCN2 administration increases in vivo activity of hippocampal CA1 pyramidal cells. (A) Circulating levels of LCN2 are highly elevated 1 h after subcutaneous injections of mouse rLCN2 and return to baseline within 24 h (n = 9 per treatment group, all males). (B) Calcium imaging experimental design (n = 2 males). (C) Representative cell map of registered neurons with outlines marking detected neurons for one day. Bar graphs represent the number of active neurons detected in each day for animal 1 (left) and animal 2 (right) under two conditions: vehicle (white) and rLCN2 treatment (purple). (D) Traces of calcium activity recorded across four days for Animal 1. Each subplot corresponds to calcium signals captured under rLCN2 (day 1 and day 3) and vehicle (day 2 and day 4) conditions. (E) Average calcium amplitude across four days for each animal (Top: animal 1; bottom: animal 2), showing differences between saline and rLCN2 conditions. (F) Predicted calcium amplitude is higher in rLCN2-injected mice compared to saline-injected mice. (G-H) Total distance traveled and mean velocity in the open field for animals 1 and 2 during calcium imaging recordings. Bars represent mean ± SEM. Point-and-whisker plot represents predicted Ca 2+ amplitude (point) and 95% confidence intervals (whiskers).

Article Snippet: Plasma and serum LCN2 levels were quantified according to the manufacturer’s protocol using a mouse lipocalin-2 ELISA kit (RayBiotech).

Techniques: Activity Assay, In Vivo, Imaging, Saline, Injection, Whisker Assay

Journal: Brain, behavior, and immunity

Article Title: Lipocalin-2 perpetuates postoperative and post-infectious neuroinflammation and anxiety-like behavior

doi: 10.1016/j.bbi.2026.106535

Figure Lengend Snippet: Chronic administration of mouse recombinant lipocalin-2 has no effect on locomotor activity and increases anxiety-like behavior in the open field. (A) Experimental timeline (n = 9 per treatment group, all males). (B-D) In the open field, the total distance traveled is comparable between groups (B) while rLCN2-injected mice spend less time in the center of the open field than the vehicle-injected mice (C). Center entries are comparable between groups (D). (E-G) In the elevated zero maze, the total distance traveled (E), time spent in the open areas (F), and open area entries (G) are similar between the vehicle and rLCN2 groups. Bars represent mean ± SEM. *p < 0.05 in two-tailed independent t-tests.

Article Snippet: Plasma and serum LCN2 levels were quantified according to the manufacturer’s protocol using a mouse lipocalin-2 ELISA kit (RayBiotech).

Techniques: Recombinant, Activity Assay, Injection, Two Tailed Test

Journal: Brain, behavior, and immunity

Article Title: Lipocalin-2 perpetuates postoperative and post-infectious neuroinflammation and anxiety-like behavior

doi: 10.1016/j.bbi.2026.106535

Figure Lengend Snippet: Brain endothelium is a major source of excess lcn2 mRNA. (A) RNAscope images of CA1 neurons and brain endothelium. (B) Quantification showing that CA1 neurons don’t express lcn2 mRNA after CLP whereas brain endothelial cells do. (C) EC-TRAP analysis showing that lcn2 is enriched in endothelial cells from murine brain, heart, kidney, liver, and lung tissues following LPS injection, represented as fold change relative to vehicle control. Bars represent mean ± SEM. RNAscope: n = 4–20 per group depending on the brain region. EC-TRAP: n = 3 mice per treatment group. P-value represents the result of a one-way ANOVA; ***p < 0.001 in two-tailed independent t-tests.

Article Snippet: Plasma and serum LCN2 levels were quantified according to the manufacturer’s protocol using a mouse lipocalin-2 ELISA kit (RayBiotech).

Techniques: RNAscope, Injection, Control, Two Tailed Test