Intraventricular clindamycin enhances interstitial brain fluid drainage and the blood–brain barrier after a traumatic brain injury

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.