FEB 07, 2018 12:00 PM PST

Refinement of a Model of Repeated Cerebrospinal Fluid Collection in Conscious Rats

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  • Clinical Veterinarian, Comparative Medicine, Basel, Roche Pharma Research and Early Development, Roche Innovation Center Basel
      Eva Maria Amen, Dr. med vet, has been working as Clinical veterinarian at F. Hoffmann-La Roche Ltd, Department of Comparative Medicine, in Basel, Switzerland since September 2011. She received her veterinary degree at the University of Veterinary Medicine in Hannover, Germany, followed by an Internship at the Small Animal Clinic and a doctoral thesis at the Department of Pathology of the same university. Since 2009 she has been working in the field of laboratory animal medicine, first at the Bayer Pharmaceutical research Center in Wuppertal, Germany, and thereafter at her current employer in Switzerland, and she is enrolled as ECLAM resident since July 2013. In her role as Clinical Veterinarian she has been supporting and advising other research functions on research with animals and providing surgical support in rat and large animal models. Born in Germany and raised in Ecuador, Eva Maria truly enjoys working in an international environment and meeting and communicating with people from all over the world.


    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.

    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.

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