Serial cerebrospinal fluid sampling in a rat model to study drug uptake from the nasal cavity

Drug transport from the nasal cavity to the brain has gained much interest in the last decade. In the present study, a model was developed to determine the uptake of drugs into the cerebrospinal fluid (CSF) after nasal delivery in rats. CSF samples were taken using a cisternal puncture method. In this method, a needle is advanced through the skin and muscles overlying the atlanto-occipital membrane into the cisterna magna, while the rat is fixed in a stereotaxic frame. This method appears to be superior over cannulation of the atlanto-occipital membrane for CSF sampling. The major advantages of the puncture method is the ability of serial and simultaneous CSF and blood sampling for over 2 h in the same rat. To obtain maximal drug absorption from the nasal cavity and uptake into CSF, different positions of the rat's head (upright-90degrees, supine-90degrees, supine-45degrees and supine-70degrees angles) were tested in nasal delivery studies using hydrocortisone (HQ as a model drug. Putting the rat in the supine-90degrees angle position increased the absorption of HC into plasma and CSF 2-fold compared to the upright-90degrees angle position. The supine-70degrees angle position did not change the HC plasma and CSF levels compared to the supine-90degrees angle position. However, the supine-70degrees angle position showed the fastest CSF sampling rate, enabling more accurate CSF sampling and therefore preferred for further studies. In conclusion, the cisternal puncture method using the supine-70degrees and 90degrees angle position is a suitable method to study drug transport from the nasal cavity into the CSF, with the ability of multiple CSF sampling. (C) 2002 Elsevier Science B.V. All rights reserved.