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A technique for intracisternal collection and administration in a rhesus macaque

Abstract

Accessing the subarachnoid space via intrathecal needle placement can be done in nonhuman primates (NHPs) and other species to collect cerebral spinal fluid (CSF) or to deliver agents into the CSF. Researchers can use a variety of techniques for intrathecal collection and administration. Drawing on various published resources and previous experience with intracisternal CSF sampling, the authors sought to modify one collection technique to include CSF administration. Here, the authors describe how they collected CSF from the cisterna magna of rhesus macaques (Macaca mulatta) and administered substances through the cisterna magna into the CSF. They identify potential concerns that they had when developing the technique and describe how they alleviated those concerns. The authors found this technique, which relies heavily on teamwork, to be an effective method for intracisternal injection of an experimental compound.

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Figure 1: Materials needed for intracisternal CSF collection and infusion.
Figure 2: Preparing a macaque for intracisternal CSF collection and infusion.
Figure 3: Positioning a macaque for intracisternal CSF collection and infusion.
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References

  1. Johanson, C.E. The choroid plexus–CSF nexus: Gateway to the brain. in Neuroscience in Medicine 2nd edn. (ed. Conn, P.M.) 165–196 (Humana, Totowa, NJ, 2003).

    Google Scholar 

  2. Driesse, M.J. et al. Distribution of recombinant adenovirus in the cerebrospinal fluid of nonhuman primates. Hum. Gene Ther. 10, 2347–2354 (1999).

    Article  CAS  Google Scholar 

  3. Driesse, M.J. et al. Intra-CSF administered recombinant adenovirus causes an immune response-mediated toxicity. Gene Ther. 7, 1401–1409 (2000).

    Article  CAS  Google Scholar 

  4. McCully, C.L., Balis, F.M., Bacher, J., Phillips, J. & Poplack, D.G. A rhesus monkey model for continuous infusion of drugs into cerebrospinal fluid. Lab. Anim. Sci. 40, 520–525 (1990).

    CAS  PubMed  Google Scholar 

  5. Dysko, R.C. & Hoskins, D.E. Medical management. in Nonhuman Primates in Biomedical Research: Biology and Management (eds. Bennett, B.T., Abee, C.R. & Henricksen, R.) 271–276 (Academic, San Diego, 1995).

    Google Scholar 

  6. Nonhuman primates. in Laboratory Animal Medicine 2nd edn. 675–791 (eds. Fox, J.G., Anderson, L.C., Loew, F.M. & Quimby, F.W.) (Academic, San Diego, 2002).

  7. Smith, M.O. & Lackner, A.A. Effects of sex, age, puncture site, and blood contamination on the clinical chemistry of cerebrospinal fluid in rhesus macaques (Macaca mulatta). Am. J. Vet. Res. 54, 1845–1850 (1993).

    CAS  PubMed  Google Scholar 

  8. Kaplan, J.R. et al. Cerebrospinal fluid monoaminergic metabolites differ in wild anubis and hybrid (Anubis hamadryas) baboons: possible relationships to life history and behavior. Neuropsychopharmacology 20, 517–524 (1999).

    Article  CAS  Google Scholar 

  9. Brady, A.G. Research techniques for the squirrel monkey (Saimiri sp.). ILAR J. 41, 10–18 (2000).

    Article  CAS  Google Scholar 

  10. Geretschläger, E., Russ, H., Mihatsch, W. & Pruzuntek, H. Suboccipital puncture for cerebrospinal fluid in the common marmoset (Callithrix jacchus). Lab. Anim. 21, 91–94 (1987).

    Article  Google Scholar 

  11. Scharf, B.A. et al. Atlanto-occipital cerebrospinal fluid collection in macaques. Toxicol. Mech. Meth. 9, 25–30 (1999).

    Article  CAS  Google Scholar 

  12. Blaney, S.M. et al. Intrathecal mafosfamide: a preclinical pharmacology and phase I trial. J. Clin. Oncol. 23, 1555–1563 (2005).

    Article  CAS  Google Scholar 

  13. Salzer, W. et al. Effect of probenecid on ventricular cerebrospinal fluid methotrexate pharmacokinetics after intralumbar administration in nonhuman primates. Cancer Chemother. Pharmacol. 48, 235–240 (2001).

    Article  CAS  Google Scholar 

  14. Ko, M.C.H., Wei, H., Woods, J.H. & Kennedy, R.T. Effects of intrathecally administered nociceptin/orphanin FQ in monkeys: behavioral and mass spectrometric studies. J. Pharmacol. Exp. Ther. 318, 1257–1264 (2006).

    Article  CAS  Google Scholar 

  15. Hagihara, Y., Saitoh, Y., Kaneda, Y., Kohmura, K. & Yoshimine, T. Widespread gene transfection into the central nervous system of primates. Gene Ther. 7, 759–763 (2000).

    Article  CAS  Google Scholar 

  16. Ko, M.C.H. et al. Intracisternal nor-binaltorphimine distinguishes central and peripheral k-opioid antinociception in rhesus monkeys. J. Pharmacol. Exp. Ther. 291, 1113–1120 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Oshima, K.M. et al. Intrathecal injection of HVJ-E containing HGF gene to cerebrospinal fluid can prevent and ameliorate hearing impairment in rats. FASEB J. 214, 212–214 (2003).

    Google Scholar 

  18. Candiani, C. et al. Pharmacokinetics of intrathecal transferrin-ricin a chain immunotoxin. Life Sci. 69, 335–346 (2001).

    Article  CAS  Google Scholar 

  19. Liu, C.H., D'Arceuil, H.E. & de Crespigny, A.J. Direct CSF injection of MnCl2 for dynamic manganese-enhanced MRI. Magn. Res. Med. 51, 978–987 (2004).

    Article  CAS  Google Scholar 

  20. Gilberto, D.B. et al. An alternative method of chronic cerebrospinal fluid collection via the cisterna magna in conscious rhesus monkeys. Contemp. Top. Lab. Anim. Sci. 42, 53–59 (2003).

    CAS  PubMed  Google Scholar 

  21. Grimes, M.A., Cameron, J.L. & Fernstrom, J.D. Cerebrospinal fluid concentrations of tryptophan and 5-hydroxyindoleacetic acid in Macaca mulatta: diurnal variations and response to chronic changes in dietary protein intake. Neurochem. Res. 25, 413–422 (2000).

    Article  CAS  Google Scholar 

  22. Reiber, H. & Schunck, O. Suboccipital puncture of guinea pigs. Lab. Anim. 17, 25–27 (1983).

    Article  CAS  Google Scholar 

  23. Kang, E.S. et al. Development of encephalopathic features similar to Reye syndrome in rabbits. Proc. Natl. Acad. Sci. USA 81, 6169–6173 (1984).

    Article  CAS  Google Scholar 

  24. Gurelik, M. et al. Cervical spinal cord stimulation improves neurological dysfunction induced by cerebral vasospasm. Neuroscience 134, 827–832 (2005).

    Article  CAS  Google Scholar 

  25. Gerber, J. et al. Metatonin is neuroprotective in experimental Streptococcus pneumoniae meningitis. J. Infect. Dis. 191, 783–790 (2005).

    Article  CAS  Google Scholar 

  26. Institute of Laboratory Animal Resources. Guide for the Care and Use of Laboratory Animals (National Academy Press, Washington, DC, 1996).

  27. Ahmed, S.V., Jayawarna, C. & Jude, E. Post lumbar puncture headache: diagnosis and management. Postgrad. Med. J. 82, 713–716 (2006).

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by grant MH062261 from the US National Institutes of Health.

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Correspondence to Karen J. Clingerman.

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The authors declare no competing financial interests.

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Clingerman, K., Spray, S., Flynn, C. et al. A technique for intracisternal collection and administration in a rhesus macaque. Lab Anim 39, 307–311 (2010). https://doi.org/10.1038/laban1010-307

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