PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Intranasal Delivery of Cell-Penetrating Therapeutic Peptide Enhances Brain Delivery, Reduces Inflammation, and Improves Neurologic Function in Moderate TBI
Version 1
: Received: 5 May 2024 / Approved: 7 May 2024 / Online: 7 May 2024 (11:13:30 CEST)
How to cite:
Yanamadala, Y.; Roy, R.; Williams, A.; Uppu, N.; Kim, A. Y.; DeCoster, M. A.; Kim, P.; Murray, T. A. Intranasal Delivery of Cell-Penetrating Therapeutic Peptide Enhances Brain Delivery, Reduces Inflammation, and Improves Neurologic Function in Moderate TBI. Preprints2024, 2024050360. https://doi.org/10.20944/preprints202405.0360.v1
Yanamadala, Y.; Roy, R.; Williams, A.; Uppu, N.; Kim, A. Y.; DeCoster, M. A.; Kim, P.; Murray, T. A. Intranasal Delivery of Cell-Penetrating Therapeutic Peptide Enhances Brain Delivery, Reduces Inflammation, and Improves Neurologic Function in Moderate TBI. Preprints 2024, 2024050360. https://doi.org/10.20944/preprints202405.0360.v1
Yanamadala, Y.; Roy, R.; Williams, A.; Uppu, N.; Kim, A. Y.; DeCoster, M. A.; Kim, P.; Murray, T. A. Intranasal Delivery of Cell-Penetrating Therapeutic Peptide Enhances Brain Delivery, Reduces Inflammation, and Improves Neurologic Function in Moderate TBI. Preprints2024, 2024050360. https://doi.org/10.20944/preprints202405.0360.v1
APA Style
Yanamadala, Y., Roy, R., Williams, A., Uppu, N., Kim, A. Y., DeCoster, M. A., Kim, P., & Murray, T. A. (2024). Intranasal Delivery of Cell-Penetrating Therapeutic Peptide Enhances Brain Delivery, Reduces Inflammation, and Improves Neurologic Function in Moderate TBI. Preprints. https://doi.org/10.20944/preprints202405.0360.v1
Chicago/Turabian Style
Yanamadala, Y., Paul Kim and Teresa Ann Murray. 2024 "Intranasal Delivery of Cell-Penetrating Therapeutic Peptide Enhances Brain Delivery, Reduces Inflammation, and Improves Neurologic Function in Moderate TBI" Preprints. https://doi.org/10.20944/preprints202405.0360.v1
Abstract
Following traumatic brain injury (TBI), secondary brain damage due to chronic inflammation is the most predominant cause of the delayed onset of mood and memory disorders. Currently no therapeutic approach is available to effectively mitigate secondary brain injury after TBI. One reason is the blood-brain barrier (BBB), which prevents passage of most therapeutic agents into the brain. Peptides have been among the leading candidates for CNS therapy due to their low immunogenicity and toxicity, bioavailability, and ease of modification. In this study, we demonstrated that non-invasive intranasal administration of KAFAK, a cell penetrating anti-inflammatory peptide, traversed the BBB in a murine model of diffuse, moderate TBI. Notably, KAFAK treatment reduced the production of pro-inflammatory cytokines that contribute to secondary injury. Furthermore, behavioral tests showed improved or restored neurological, memory, and locomotor performance in KAFAK-treated mice. This study demonstrates KAFAK's ability to cross the blood-brain barrier, to lower pro-inflammatory cytokine levels in vivo, and to restore function after a moderate TBI.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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