Hydrocephalus occurs because of a dysfunction in the CSF flow and dynamics resulting in enlarged brain ventricles (ventriculomegaly). It is a global health concern which affects people of all ages, with the elderly having the highest prevalence of any age group. Normal pressure hydrocephalus (NPH) is the common form that affects this population, and it could be idiopathic or stem from secondary causes. NPH is most often misdiagnosed or underdiagnosed because its pathophysiology is poorly understood and the NPH symptoms mimic other neurodegenerative diseases of aging. Research in this field is hampered because there are no applicable animal models. Thus, this study is aimed at investigating a novel model of NPH in rats that may be used to better understand NPH pathophysiology and develop biomarkers and therapies for this disorder. Our laboratory has extensively characterized a pediatric rat model of hydrocephalus, the Transmembrane 67 (TMEM67) rats. Our TMEM67-/- rats have been shown to develop severe hydrocephalus and do not survive past post-natal (P) day21. The TMEM67+/- litter mates, the obligate breeders, appear healthy and generally survive past 1 year. We have preliminary studies that indicate these animals may express a mild form of hydrocephalus. Thus, our hypothesis is that the TMEM67+/- rats display a form of adult hydrocephalus that develops over time leading to a type of progressive hydrocephalus like NPH. To investigate this, the experimental rats were grouped into wildtype (WT) controls and TMEM67+/- rats, and MRI scans were taken to assess ventricular volumes. The lateral ventricular volumes were determined using signal-threshold- and manual- based segmentation from regions of interest drawn on each lateral ventricles-containing slice using Imalytics Preclinical software (Gremse-IT GmbH, Germany). The non-parametric Mann-Whitney U test was used to assess any significant differences in lateral ventricle volume between WT and TMEM67+/- rats, with a 5% level of significance. The results of the MRI scans show that the adult TMEM67+/- lateral ventricular volumes were significantly higher than those of the WT. This suggests a form of adult hydrocephalus. To track the developmental changes in the ventricles of WT and TMEM67+/- rats, scans were taken at different timepoints. The postnatal (P)15, P30, P45 data show an exponential rate of growth in the TMEM67+/- rats compared to the linear growth in the WT. This points to hydrocephalus progression accompanied by growth and aging. Further studies will explore if the TMEM67+/- adult rats display the characteristic NPH triad; gait impairment, cognitive dysfunction and urinary incontinence, and measure intracranial pressure as well as track the rate of growth in the ventricles as they age across additional time points. This research was conducted with the support of Congressional Directed Medical Research Program Grants #HT94252310296 and #HT94252310401 (BBY). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Obiako et al. (Fri,) studied this question.