Intraventricular dimethyl sulfoxide (DMSO) induces hydrocephalus in a dose-dependent pattern

Introduction: Dimethyl sulfoxide (DMSO), a widely utilized solvent in the medical industry, has been associated with various adverse effects, even at low concentrations, including damage to mitochondrial integrity, altered membrane potentials, caspase activation, and apoptosis. Notably, therapeutic molecules for central nervous system treatments, such as embolic agents or some chemotherapy drugs that are dissolved in DMSO, have been associated with hydrocephalus as a secondary complication. Our study investigated the potential adverse effects of DMSO on the brain, specifically focusing on the development of hydrocephalus and the effect on astrocytes. Methods: Varied concentrations of DMSO were intraventricularly injected into 3-day-old mice, and astrocyte cultures were exposed to similar concentrations of DMSO. After 14 days of injection, magnetic resonance imaging (MRI) was employed to quantify the brain ventricular volumes in mice. Immunofluorescence analysis was conducted to delineate DMSO-dependent effects in the brain. Additionally, astrocyte cultures were utilized to assess astrocyte viability and the effects of cellular apoptosis. Results: Our findings revealed a dose-dependent induction of ventriculomegaly in mice with 2%, 10%, and 100% DMSO injections (p < 0.001). The ciliated cells of the ventricles were also proportionally affected by DMSO concentration (p < 0.0001). Furthermore, cultured astrocytes exhibited increased apoptosis after DMSO exposure (p < 0.001). Conclusion: Our study establishes that intraventricular administration of DMSO induces hydrocephalus in a dose-dependent manner. This observation sheds light on a potential explanation for the occurrence of hydrocephalus as a secondary complication in intracranial treatments utilizing DMSO as a solvent.