# A neuroprotective tetrapeptide for treatment of acute traumatic brain injury

**Authors:** Aman P Mann, Sazid Hussain, Pablo Scodeller, Hope N B Moore, Elan Sherazee, Rachel M Russo, Erkki Ruoslahti

PMC · DOI: 10.1038/s44321-025-00312-5 · EMBO Molecular Medicine · 2025-10-01

## TL;DR

A new tetrapeptide called CAQK shows promise in reducing brain damage and improving recovery after traumatic brain injury in mice and pigs.

## Contribution

The study introduces CAQK as a novel therapeutic candidate for acute traumatic brain injury with demonstrated neuroprotective effects.

## Key findings

- CAQK reduces injury size and neuroinflammation in TBI mice.
- CAQK improves motor and cognitive function in TBI mice without toxicity.
- CAQK accumulates in injured brain tissue and targets injuries in large animal models.

## Abstract

Traumatic brain injury (TBI) is a major clinical problem because of the high incidence and the severity of the subsequent sequelae. Despite extensive efforts, there are no therapeutic drugs clinically approved for treating acute TBI patients. To address this unmet need, we assessed the activity of the tetrapeptide, CAQK, in mice. When administered intravenously shortly after moderate or severe TBI, CAQK accumulates in the injured brain in mice and pigs. CAQK binds to an extracellular matrix glycoprotein complex that is upregulated in injured brain. Treatment of TBI mice with CAQK resulted in reduction in the size of the injury compared to control mice. There was reduced upregulation of the glycoprotein complex, less apoptosis, and lower expression of inflammatory markers in the injured area, indicating that CAQK alleviates neuroinflammation and the ensuing secondary injury. CAQK treatment also improved functional deficit in TBI mice, with no overt toxicity. Our findings suggest that CAQK may have therapeutic applications in TBI.

Secondary injury following a primary impact to the brain is a critical determinant of complications and disability after traumatic brain injury (TBI). CAQK peptide reduces secondary injury in TBI.

Treatment with CAQK peptide in mouse model of TBI results in reduction of neuroinflammation and apoptosis.CAQK treated mice with TBI also showed partial recovery in motor and cognitive deficits associated with TBI.CAQK shows no toxicity and targets injuries in large animal models extending its application as a potential therapeutic candidate for acute injuries of the nervous system.

Treatment with CAQK peptide in mouse model of TBI results in reduction of neuroinflammation and apoptosis.

CAQK treated mice with TBI also showed partial recovery in motor and cognitive deficits associated with TBI.

CAQK shows no toxicity and targets injuries in large animal models extending its application as a potential therapeutic candidate for acute injuries of the nervous system.

Secondary injury following a primary impact to the brain is a critical determinant of complications and disability after traumatic brain injury (TBI). CAQK peptide reduces secondary injury in TBI.

## Linked entities

- **Diseases:** traumatic brain injury (MONDO:0858950)
- **Species:** Mus musculus (taxon 10090), Sus scrofa (taxon 9823)

## Full-text entities

- **Diseases:** toxicity (MESH:D064420), neuroinflammation (MESH:D000090862), brain (MESH:D001927), inflammatory (MESH:D007249), functional deficit (MESH:D001289), TBI (MESH:D000070642)
- **Chemicals:** CAQK (-)
- **Species:** Sus scrofa (pig, species) [taxon 9823], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12603041/full.md

## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC12603041/full.md

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Source: https://tomesphere.com/paper/PMC12603041