Introduction:
The cannulation of the cisterna magna in the rat is a valuable model for in-vivo sampling of cerebrospinal fluid for studying delivery of new drugs into the central nervous system or disease models. It offers the advantages of repeated sampling without anesthesia-induced bias and using animals as their own controls.

Materials and Methods:
An established model was retrospectively reviewed for outcome and it was hypothesized that by refining the method i.e. by 1) implementing pathophysiological based anesthesia & analgesia, 2) using state of the art peri-operative monitoring and supportive care, 3) increasing stability of the cement-cannula assembly, and 4) selecting a more adapted animal strain, the outcome of the model – quantified by peri-operative mortality, survival time and stability of the implant- could be improved and enhance animal welfare.

Results:
After refinement of the technique, perioperative mortality significantly dropped (7 animals out of 73 compared to 4 out of 322; p=0.001), survival time significantly increased (36±14 compared to 28±18 days; p<0.001), as well as the stability of the cement-cannula-assembly (47±8 days of adhesion compared to 33±15 days and 34±13 days with two other cement types; p<0.001).

Discussion and Conclusions:
Overall, the concept of the 3 Rs by Russel and Burch was successfully addressed and animal welfare improved by: 1) reducing the total number of animals needed thanks to lower mortality or euthanasia due to technical failure and increased usage time frame of the individual rats; 2) improving the scientific quality of the model.