Blood and CSF Markers
Fluid-based biomarkers are being widely used in clinical trials of CNS diseases. Many of these biomarkers are also present in animal models of these disease. At Biospective, we can work with you to analyze a range of biomarkers from blood and CSF of rodent models.
One example of a clinically translational fluid biomarker is neurofilament light (NfL). We routinely use the ultrasensitive Simoa assay to measure NfL levels in the plasma and CSF from many of our rodent models, including our alpha-synuclein models of Parkinson's disease, our TDP-43 mouse model of ALS, and our EAE mouse model of multiple sclerosis.
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What is Simoa?
Simoa® stands for Single Molecule Array. It is is an ultrasensitive immunoassay technology that allows for detection of biomarkers, such as proteins, at very low levels. With Simoa, one can achieve sensitivity that is orders of magnitude higher than standard sandwich-based immunoassay techniques, detecting as little as femtogram (fg/mL) concentrations, while consuming as little as 1 µL of sample. As such, this ultrasensitive detection capability allows for the quantification of biomarkers at concentrations that have previously been difficult or impossible to measure.
What is Neurofilament Light?
Neurofilament Light (or NfL) is a cytoskeletal protein that is highly specific for neurons. While NfL is normally present is low levels in body fluids due to slow turnover in neurons, it is released from neurons due to injury or disease, thereby resulting in increased levels in the CSF and/or blood. NfL can be measured in fluids, such as plasma, serum, and CSF by sensitive assays, such as Simoa.
How much CSF does a mouse have?
It has been estimated that mice have 35-40 µL of CSF, which replenishes rapidly at a rate of 0.32-0.35 µL/min, turning over the total CSF volume 12-14 times per day (Fowler et al., Adv. Drug Deliv. Rev., 165–166: 77-95, 2020; doi: 10.1016/j.addr.2020.02.006).
How much CSF can be collected from a mouse?
We collect CSF from the cisterna magna. We can typically obtain ~5-10 µL for each sample collection.
Can Biospective obtain in-life CSF samples?
Yes. Our team has developed the ability to collect CSF from mice during the in-life portion of the study. This ability allows us to follow specific biomarkers, such as neurofilament light (NfL), over time or measure different biomarkers (e.g. cytokines, misfolded proteins) in the same mouse.