# Food-based multisensory stimulation ameliorates cognitive impairment after mild traumatic brain injury in male rats by modulating intestinal and brain inflammation

**Authors:** Yuhan Wei, Hanif Ullah, Guangneng Liao, Xue Xiao, Jiang Yao, Qiujing Du, Qijie Li, Ka Li, Eric Anthony Sribnick, Eric Anthony Sribnick, Eric Anthony Sribnick, Eric Anthony Sribnick

PMC · DOI: 10.1371/journal.pone.0343814 · PLOS One · 2026-02-27

## TL;DR

A food-based sensory stimulation approach improves cognitive function in rats with mild traumatic brain injury by reducing inflammation in the gut and brain.

## Contribution

This study introduces food-based multisensory stimulation as a novel non-invasive treatment for cognitive impairment after mTBI.

## Key findings

- Multisensory stimulation improved spatial and recognition memory in mTBI rats.
- Sensory stimulation restored gut microbiota balance and increased anti-inflammatory SCFAs like butyrate.
- Butyrate reduced neuroinflammation and preserved neuronal density in the hippocampus and cortex.

## Abstract

Mild traumatic brain injury (mTBI) often leads to cognitive impairment (CI), with neuroinflammation and gut microbiota dysbiosis playing pivotal roles in its pathogenesis. This study aimed to investigate whether food-based multisensory stimulation could ameliorate cognitive deficits in mTBI rats via modulation of the gut–brain axis. Using a rat model of mTBI, we demonstrated that food-based multisensory stimulation significantly improved spatial and recognition memory, as evidenced by performance in the Morris water maze and novel object recognition tests, and reduced serum biomarkers of neurological injury (NSE, S100β). Gut microbiota analysis revealed that sensory stimuli restored microbial balance, increasing beneficial taxa such as Ruminococcaceae and reducing pathogenic genera such as Alistipes, Prevotella. Concurrently, senso.ry stimulation increased fecal and serum levels of short-chain fatty acids (SCFAs), particularly butyrate, which were associated with reduced gut and neuroinflammation. In vitro, butyrate supplementation exhibited significant anti-inflammatory effects, promoting M2 microglial polarization and reducing pro-inflammatory cytokines (TNF-α, IL-1β). Histological analyses further revealed neuroprotective effects, preserving neuronal density in the hippocampus and cortex. These findings suggest that multisensory stimulation may mitigate CI post-mTBI by restoring gut microbiota homeostasis, enhancing butyrate production, and attenuating neuroinflammation. This non-invasive approach holds promise for cognitive rehabilitation in patients with mTBI, although further research is needed to elucidate its long-term effects and translational potential.

## Linked entities

- **Chemicals:** butyrate (PubChem CID 104775)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Ca3 (carbonic anhydrase 3) [NCBI Gene 54232] {aka Car3}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, HP (haptoglobin) [NCBI Gene 3240] {aka HP2ALPHA2, HPA1S}, NEFL (neurofilament light chain) [NCBI Gene 4747] {aka CMT1F, CMT2E, CMTDIG, NF-L, NF68, NFL}, Il4 (interleukin 4) [NCBI Gene 287287] {aka Il4e12}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Eno2 (enolase 2) [NCBI Gene 24334] {aka NSE, RNEN3}, Crp (C-reactive protein) [NCBI Gene 25419] {aka Aa1249, Ab1-341, Ab2-196, Ac1-114, Ac1262, Ac2-069}, Ffar2 (free fatty acid receptor 2) [NCBI Gene 292794] {aka Gpr43}, Lep (leptin) [NCBI Gene 25608] {aka OB, obese}, S100b (S100 calcium binding protein B) [NCBI Gene 25742] {aka S100P}, Hcrt (hypocretin neuropeptide precursor) [NCBI Gene 25723] {aka orexin-A}, Ffar3 (free fatty acid receptor 3) [NCBI Gene 365228] {aka Gpr41}, TREM2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 54209] {aka AD17, PLOSL2, TREM-2, Trem2a, Trem2b, Trem2c}, Cd86 (CD86 molecule) [NCBI Gene 56822] {aka B7-2}, CHI3L1 (chitinase 3 like 1) [NCBI Gene 1116] {aka ASRT7, CGP-39, GP-39, GP39, HC-gp39, HCGP-3P}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Actb (actin, beta) [NCBI Gene 81822] {aka Actx}
- **Diseases:** overweight (MESH:D050177), obese (MESH:D009765), sensorimotor impairments (MESH:D020233), Visceral pain (MESH:D059265), weight drop (MESH:D020427), Neurological deficits (MESH:D009461), ischemia (MESH:D007511), primary progressive aphasia (MESH:D018888), Metabolic Syndrome (MESH:D024821), Inflammation (MESH:D007249), Cephalalgia (MESH:D006261), anxiety (MESH:D001007), neuroinflammation (MESH:D000090862), CTX (MESH:D000303), TBI (MESH:D000070642), dysbiosis (MESH:D064806), Alzheimer's disease (MESH:D000544), constipation (MESH:D003248), systemic (MESH:D015619), dementia (MESH:D003704), depression (MESH:D003866), neuronal damage (MESH:D009410), deficits in spatial learning and memory (MESH:D008569), weight-drop injury (MESH:D000094222), sepsis (MESH:D018805), CI (MESH:D003072), Migraine (MESH:D008881), dislocation (MESH:D004204), neurological injuries (MESH:D020196), Brain Injury (MESH:D001930), -liver-brain axis dysfunction (MESH:D001927), mTBI (MESH:D001924), infections (MESH:D007239), and brain inflammation (MESH:D004660)
- **Chemicals:** propionic acid (MESH:C029658), TRIzol (MESH:C411644), isoflurane (MESH:D007530), water (MESH:D014867), toluidine blue (MESH:D014048), ethanol (MESH:D000431), acetic acid (MESH:D019342), paraffin (MESH:D010232), streptomycin (MESH:D013307), corticosterone (MESH:D003345), quercetin (MESH:D011794), xylene (MESH:D014992), agarose (MESH:D012685), sucrose (MESH:D013395), lipid (MESH:D008055), paraformaldehyde (MESH:C003043), LPS (MESH:D008070), butyric acid (MESH:D020148), CO2 (MESH:D002245), Prebiotics (MESH:D056692), sulfuric acid (MESH:C033158), SCFA (MESH:D005232), 4',6-diamidino-2-phenylindole (MESH:C007293), chitosan lactate (MESH:C000720764), glucose (MESH:D005947), diethyl ether (MESH:D004986), Betadine Solution (MESH:D011206), alcohol (MESH:D000438), Eosin (MESH:D004801), acetate (MESH:D000085), Hematoxylin (MESH:D006416), penicillin (MESH:D010406), 2,2-dimethylbutyric acid (MESH:C074677), bile acid (MESH:D001647), H&amp;E (MESH:D006371), D-Lac (-), fatty acid (MESH:D005227), propionate (MESH:D011422), trichloroacetic acid (MESH:D014238), sodium sulfate (MESH:C012036), Butyrate (MESH:D002087)
- **Species:** Ruminococcus (genus) [taxon 1263], Roseburia (genus) [taxon 841], Faecalibacterium (genus) [taxon 216851], Lactobacillus (genus) [taxon 1578], Mus musculus (house mouse, species) [taxon 10090], Prevotella (genus) [taxon 838], gut metagenome (species) [taxon 749906], Gallus gallus (bantam, species) [taxon 9031], Eubacterium xylanophilum (species) [taxon 39497], Homo sapiens (human, species) [taxon 9606], Bifidobacterium (genus) [taxon 1678], Rattus norvegicus (brown rat, species) [taxon 10116], Alistipes (genus) [taxon 239759]
- **Cell lines:** BV2 — Mus musculus (Mouse), Transformed cell line (CVCL_0182)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12948070/full.md

## References

61 references — full list in the complete paper: https://tomesphere.com/paper/PMC12948070/full.md

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Source: https://tomesphere.com/paper/PMC12948070