Choroid plexus ablation in neonatal mice cuts ventricular volume in an age-dependent window

Deleting the choroid plexus in newborn mice can durably shrink the brain’s fluid-filled ventricles, but only if the intervention lands within a narrow developmental window, according to a new study in Fluids and Barriers of the CNS. The work, published on 17 October 2026, tested whether removing the brain’s main source of cerebrospinal fluid could offer an alternative to the invasive surgeries currently used for neonatal hydrocephalus.

The choroid plexus sits inside the cerebral ventricles and produces roughly 80 percent of cerebrospinal fluid. When fluid volume becomes dysregulated, the result can be neonatal hydrocephalus, a condition estimated to affect 0.1 to 0.6 percent of children. Current treatments are invasive and carry high risks of complications and repeated surgical interventions, which the authors cite as the motivation for exploring strategies that target fluid production itself rather than draining it.

The team used a genetically engineered mouse line, the iDTR mouse, in which cells can be killed by diphtheria toxin. In previous work, the researchers showed that diphtheria toxin induces choroid plexus epithelial cell loss and permanent cerebrospinal fluid volume loss in adult iDTR mice. The new study extended this approach to early postnatal stages, which had remained unexplored.

The timing of the intervention proved decisive. Multiple diphtheria toxin injections given between postnatal days 4 and 6, or a single injection at postnatal day 10, significantly reduced ventricular volume by postnatal day 30. In contrast, single injections given before postnatal day 8 had no effect on ventricular volume. The study therefore defines an age- and dose-dependent window of choroid plexus vulnerability in these mice.

Histological and gene expression analyses revealed that the damage to the choroid plexus itself unfolded in an age-dependent manner. The treatment disrupted epithelial cells, increased choroid plexus epithelial cell death, produced long-term changes in choroid plexus gene expression patterns, and caused a significant reduction in total choroid plexus size. The authors also note possible reactive mechanisms that follow choroid plexus removal and the reduction of fluid production in the neonatal brain.

Importantly, the reported ventricular volume reduction was robust and permanent, and the intervention did so without altering intracranial pressure or global brain transcriptomes, according to the study’s significance statement. These observations in mice suggest that the choroid plexus can be removed without triggering the pressure changes or widespread transcriptional disruption that might otherwise undermine such an approach.

To test relevance beyond the engineered model, the researchers applied the same early postnatal choroid plexus epithelial loss in the prh neonatal hydrocephalus mouse model, a genetic model of the condition. The intervention reduced ventricular volume in this model and temporally improved survival, which the authors present as evidence of the translational relevance of choroid plexus-targeted therapies.

The findings, the authors write, highlight the clinical feasibility of long-term cerebrospinal fluid volume control via choroid plexus removal in the developing brain, and provide experimental support for choroid plexus-directed strategies as an alternative long-term treatment for neonatal hydrocephalus. The study is an open-access research article, and the version shared at publication is the accepted manuscript, subject to further edits before the final version of record.

As with all preclinical rodent work, the results are experimental and do not establish a treatment for children. The diphtheria toxin approach depends on a genetic modification that cannot be applied clinically, and the age-dependent window identified in iDTR mice may not map directly onto human development. Nevertheless, by showing that the choroid plexus can be targeted during early postnatal life to produce lasting ventricular volume reduction, the study adds a concrete experimental foundation to a therapeutic concept that has long remained poorly defined.

Subject of Research: Age-dependent choroid plexus ablation in neonatal mice as an experimental strategy for reducing cerebrospinal fluid volume in neonatal hydrocephalus.

Article Title: Neonatal diphtheria toxin treatment of iDTR mice reduces ventricular volume and shows damage in the choroid plexus in an age-dependent manner

Article References: Merchan-Sala, P., Siddiqui, Z., Stephens, S. A., Sheikh, O. N., Bandaras, L., Yamamoto, R., Duru, S., Prudente, A. S., D’Souza, S. P., Fugate, E. M., Lim, H.-W., Shula, C., Brown, F. N., Iwasawa, E., Sebring, G., Shah, V., Berta, T., Lindquist, D., Mangano, F. T., & Goto, J. (2026). Neonatal diphtheria toxin treatment of iDTR mice reduces ventricular volume and shows damage in the choroid plexus in an age-dependent manner. Fluids and Barriers of the CNS. https://doi.org/10.1186/s12987-026-00889-0

Image Credits: AI Generated

DOI: 10.1186/s12987-026-00889-0

Keywords: choroid plexus, cerebrospinal fluid, neonatal hydrocephalus, ventricular volume, diphtheria toxin, iDTR mice, prh mouse model, CSF production, postnatal brain development, epithelial cell ablation, Neonatal, diphtheria