Collection of cerebrospinal fluid from murine lateral ventricles for biomarker determination in mucopolysaccharidosis type IIIA

Abstract

BackgroundCerebrospinal fluid (CSF) collection is currently the only feasible means to obtain biological fluid for the quantitative determination of biomarkers that may reflect disease activity within the brain. Studies in mouse models of human neurological disease benefit from ascertainment and subsequent analysis of brain tissue that is not afforded in human patients. The CSF provides a translational forum, however, due to the practical constraints presented by the mouse’s small size, CSF is often ignored in experimental mouse models. New methodHere we report a method for the controlled, precise and predictable collection of 10 μL of CSF from the lateral ventricles of adult mice using stereotaxic equipment and a micro-syringe pump. ResultsCollected CSF was clear and manifested the consistency of water and moreover, quantification of a disease-specific biomarker for the neurodegenerative disorder, mucopolysaccharidosis type IIIA (MPS IIIA) was possible in this small volume of CSF. In the naturally occurring mouse model of MPS IIIA, that faithfully recapitulates the human form of the disease, this biomarker was present at concentrations of >100 pmol/mL and undetectable in wild-type mice. Comparison with existing methodAdvantages of this method over the most commonly used cisterna magna collection technique include increased CSF sample volume (10 μL) and reduced blood contamination. ConclusionThe ability to collect CSF from mouse models of neurological disease enables a forum for translating research outcomes in experimental models to the human equivalent in which CSF collection is also possible.