# Impact of fracture fixation surgery on cognitive function and the gut microbiota in mice with a history of stroke

**Authors:** Yu Lu, Zixuan Li, Rukun Xu, Yajie Xu, Wenwen Zhang, Yong Zhang, Zhaojing Fang, Cailong Pan, Xiaoliang Wang

PMC · DOI: 10.1515/biol-2022-1061 · Open Life Sciences · 2025-02-25

## TL;DR

This study shows that fracture surgery worsens cognitive function in mice with a history of stroke, possibly by changing gut bacteria and increasing inflammation.

## Contribution

The study reveals a novel link between fracture surgery, gut microbiota changes, and cognitive decline in post-stroke mice.

## Key findings

- TFIF surgery significantly impaired cognitive function in stroke mice compared to controls.
- Gut microbiota beta diversity changed after surgery, but alpha diversity remained stable.
- Surgery increased brain inflammation and altered gut inflammation markers like IL-1β and LPS.

## Abstract

Perioperative cognitive dysfunction is a common complication in stroke patients undergoing secondary surgeries. This study investigated the effects of tibial fracture internal fixation (TFIF) surgery on cognitive function and the gut microbiota in mice with a history of stroke. Using the middle cerebral artery occlusion method to induce stroke, we assessed cognitive function via the fear conditioning test and analyzed the gut microbiota through 16S rRNA sequencing. Compared with those in the normal and stroke groups, the cognitive function of the mice in the stroke group that underwent TFIF surgery was significantly impaired. Gut microbiota analysis revealed significant changes in beta diversity, but not in alpha diversity, in these mice. Additionally, TFIF surgery increased microglial activation and IL-1β and lipopolysaccharide (LPS) levels in the brain while reducing α-defensin levels and increasing IL-1β and LPS levels in the colon. These results suggest that TFIF surgery exacerbates cognitive impairment in stroke mice, possibly through alterations in the gut microbiota that impair intestinal defense and promote inflammation. This study highlights the critical role of the gut microbiome in cognitive function and perioperative outcomes, offering insights into potential therapeutic strategies for perioperative cognitive dysfunction in stroke patients.

## Linked entities

- **Proteins:** IL1B (interleukin 1 beta), IRF6 (interferon regulatory factor 6)
- **Diseases:** stroke (MONDO:0005098)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}
- **Diseases:** tibial fracture (MESH:D013978), cognitive dysfunction (MESH:D003072), stroke (MESH:D020521), fracture (MESH:D050723), middle cerebral artery occlusion (MESH:D020244), inflammation (MESH:D007249)
- **Chemicals:** LPS (MESH:D008070)
- **Species:** Homo sapiens (human, species) [taxon 9606], gut metagenome (species) [taxon 749906], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC11868713