Insulin increases central apolipoprotein E levels as revealed by an improved technique for collection of cerebrospinal fluid from rats

Cerebrospinal fluid (CSF) provides an invaluable analytical window to the central nervous system (CNS) because it reflects the dynamically changing complement of CNS constituents. We describe an improved method for sampling CSF in rats that is easy to perform. It has a 96% success rate of CSF collection and consistently yields large volumes (150–200 μl) of CSF. The blood contamination rate is also low (6%) as determined by both visual inspection and the lack of molecular detection of apolipoprotein B, a plasma-derived protein, which is absent in the CNS. This improved method of CSF sampling can have broad applicability in physiological and pharmacological evaluation for diverse CNS targets. We used this technique to provide proof of principle by examining the effect of intraperitoneal insulin on the level of apolipoprotein E (apoE) in the CSF. Insulin (0.5 and 1 U/kg) led to a significant increase of insulin in both plasma and CSF at 2 h after intraperitoneal administration and decreased blood glucose for at least 2 h. ApoE concentrations in CSF, but not in plasma, were also significantly increased, and its time-course was inversely correlated with the alterations in blood glucose over 2 h. These results provide a pharmacological validation of the novel CSF sampling and validation procedure for sampling rat CSF.

► We describe an improved method for sampling CSF in rats. ► This technique has a 96% success rate and yields up to 200 μl of CSF within 12 min. ► Blood contamination rate is low (6%), and a molecular examination of apoB is used to detect trace amounts of blood contamination in CSF samples. ► Using this technique, we demonstrated that ip insulin significantly increased apolipoprotein E level in rat CSF. ► This improved method can have broad applicability in physiological and pharmacological evaluation for diverse CNS targets.