Optimisation of ExoCounter technology for use in cerebrospinal fluid and investigation of placenta-derived exosomes within cerebrospinal fluid

Pregnancy is associated with neurological changes and increased risk of certain neurological pathologies. The mechanisms and causes of these changes are not entirely clear. Placenta-derived exosomes are small vesicles released from the placenta into maternal circulation. Research suggests that these exosomes are bioactive and can affect cells and tissues they encounter. There is evidence that exosomes of non-placental origin can cross the blood-brain barrier and be taken up by central nervous tissues, and that placenta-derived exosomes may increase the permeability of the blood-brain barrier. At the time of writing, no human studies have addressed the possibility that placenta-derived exosomes may cross the blood-brain barrier and affect neurological tissues. This project used a novel technology for exosome quantification, the ExoCounter assay, to analyse placenta-derived exosomes in matched cerebrospinal fluid and plasma samples from normotensive, preeclamptic and eclamptic pregnant women. This project did not find evidence that placenta-derived exosomes are present in cerebrospinal fluid. No difference was seen in plasma or cerebrospinal fluid counts between the three clinical groups, but this was affected by small samples sizes and unmatched gestational age between groups. In addition to work on the samples, this project assessed performance of the ExoCounter assay, and found high linearity, high repeatability, and dependence of the assay on intact exosome membranes. The impact of human/pipetting error and human anti-mouse antibodies was assessed, with no evidence found of interference by either factor.