Intraventricular clindamycin enhances interstitial brain fluid drainage and the blood–brain barrier after a traumatic brain injury
9 affiliations
- 1Department of Neurosurgery, The University of Texas at Austin, Austin, TX 78712
- 2Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712
- 3Oden Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX 78712
- 4Cancer Research Center, The University of Texas at Austin, Austin, TX 78712
- 5Department of Diagnostic Medicine, The University of Texas at Austin, Austin, TX 78712
- 6Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030
- 7Department of Neurology, The University of Texas at Austin, Austin, TX 78712
- 8Department of Psychology, The University of Texas at Austin, Austin, TX 78712
- 9Mulva Clinic for the Neurosciences, The University of Texas at Austin, Austin, TX 78712
Abstract
Despite advances in the acute clinical management of severe traumatic brain injuries (TBIs), treating injury-derived secondary pathogenesis remains challenging. We demonstrate intracerebroventricular (I.C.V.) administration of clindamycin alleviates TBI secondary pathogenesis in both focal and diffuse murine models of brain injury. I.C.V. administration of clindamycin increased the motility of ependymal cilia, which line the ventricles and spinal canal, by 30 to 60%, which correlated with interstitial brain fluid drainage through the cortex (r > 0.9 Pearson, n = 4 compounds tested). I.C.V. clindamycin treatment post-TBI also restored the blood–brain barrier (BBB), decreased lesion size, and lowered serum levels of glial fibrillary acidic protein by 2.8-fold. Consistent with these data, a novel objective recognition test revealed an improvement in recognition memory in brain-injured mice treated with clindamycin. These collective findings reveal a counterintuitive finding that I.C.V. clindamycin enhances drainage of toxins from the brain while simultaneously restoring the BBB, potentially providing a new solution for alleviating secondary pathogenesis in brain-injured patients.
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BibTeX
@article{ashby2026intraventricular,
title = {{Intraventricular clindamycin enhances interstitial brain fluid drainage and the blood–brain barrier after a traumatic brain injury}},
author = {Landon S. Ashby and Megan G. Crowe and Daveraj Chakravarty and Sanjeev Medam and Gabriel Frampton and Ayesha B. Das and David A. Hormuth and Thomas E. Yankeelov and Vincent Y. C. Wang and Linda J. Noble-Haeusslein and Benjamin J. Umlauf},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2536755123},
url = {https://doi.org/10.1073/pnas.2536755123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Intraventricular clindamycin enhances interstitial brain fluid drainage and the blood–brain barrier after a traumatic brain injury
AU - Landon S. Ashby
AU - Megan G. Crowe
AU - Daveraj Chakravarty
AU - Sanjeev Medam
AU - Gabriel Frampton
AU - Ayesha B. Das
AU - David A. Hormuth
AU - Thomas E. Yankeelov
AU - Vincent Y. C. Wang
AU - Linda J. Noble-Haeusslein
AU - Benjamin J. Umlauf
PY - 2026
DA - 2026/10/27
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2536755123
UR - https://doi.org/10.1073/pnas.2536755123
AB - Despite advances in the acute clinical management of severe traumatic brain injuries (TBIs), treating injury-derived secondary pathogenesis remains challenging. We demonstrate intracerebroventricular (I.C.V.) administration of clindamycin alleviates TBI secondary pathogenesis in both focal and diffuse murine models of brain injury. I.C.V. administration of clindamycin increased the motility of ependymal cilia, which line the ventricles and spinal canal, by 30 to 60%, which correlated with interstitial brain fluid drainage through the cortex (r > 0.9 Pearson, n = 4 compounds tested). I.C.V. clindamycin treatment post-TBI also restored the blood–brain barrier (BBB), decreased lesion size, and lowered serum levels of glial fibrillary acidic protein by 2.8-fold. Consistent with these data, a novel objective recognition test revealed an improvement in recognition memory in brain-injured mice treated with clindamycin. These collective findings reveal a counterintuitive finding that I.C.V. clindamycin enhances drainage of toxins from the brain while simultaneously restoring the BBB, potentially providing a new solution for alleviating secondary pathogenesis in brain-injured patients.
SN - 0027-8424
SN - 1091-6490
ER -