Impact of intraperitoneal lipopolysaccharide exposure regimens on spatial learning performance on the final day of Morris Water Maze training in Wistar rats: a systematic review and meta-analysis.

Authors

Elizama de Gregório, Lincon Bordignon Somensi, Weber Claudio Nunes da Silva

Published in

Behavioural brain research. Pages 116547. Oct 27, 2026. Epub Oct 27, 2026.

Abstract

Lipopolysaccharide (LPS) is widely used to induce neuroinflammation in preclinical models; however, variability in dosing protocols and exposure regimens limits methodological standardization and comparability across studies.
To quantify the effect of intraperitoneal LPS administration on Morris water maze performance during the acquisition phase in adult male Wistar rats and to investigate whether training duration, LPS exposure regimen, and dose contribute to variability in the observed effects.
A systematic review with meta-analysis was conducted in accordance with the PRISMA guidelines. The search included the databases PubMed/MEDLINE, Embase, Web of Science, Scopus, the Cochrane Library, and the Brazilian Digital Library of Theses and Dissertations. We included experimental studies involving adult male Wistar rats administered LPS intraperitoneally and evaluated in the Morris water maze using training protocols lasting 4 to 5 days. The primary outcome was escape latency on the last day of training. SYRCLE's Risk of Bias Tool was used to assess the risk of bias in the included studies. Analyses were conducted using a random-effects model, employing the standardized mean difference.
Nineteen studies met the inclusion criteria. The primary unstratified random-effects meta-analysis showed that intraperitoneal LPS administration was associated with significantly prolonged escape latency on the final day of MWM acquisition (Hedges' g = 1.95; SE = 0.27; 95% CI: 1.42-2.48; p < 0.001), with substantial heterogeneity (I² = 76.7%). Sensitivity analysis using raw mean differences indicated an average increase of 14.03s in escape latency, and leave-one-out analysis showed that the pooled effect remained significant after the exclusion of each individual study. Formal subgroup comparisons showed no statistically significant differences according to MWM training duration (p = 0.054), LPS exposure regimen (p = 0.135), or dose category (p = 0.284). Evidence of publication bias was detected.
Intraperitoneal LPS administration consistently prolongs escape latency and impairs performance during the acquisition phase of the Morris water maze in adult male Wistar rats. However, because escape latency may also be influenced by motor, motivational, and sickness-related factors, these findings should not be interpreted as unequivocal evidence of impaired spatial learning. Training duration, exposure regimen, and dose category did not significantly moderate the observed effect, highlighting the likely contribution of additional methodological sources of heterogeneity.

PMID:
42946062
Bibliographic data and abstract were imported from PubMed on 28 Oct 2026.

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