Rat Cerebrospinal Fluid Treatment Method through Cisterna Cerebellomedullaris Injection

  • Thainá Garbino dos Santos
  • Mery Stéfani Leivas Pereira
  • Diogo Losch Oliveira
Method
  • 46 Downloads

Abstract

Drugs that lack the ability to cross the blood-brain barrier (BBB) need to be placed directly into the central nervous system. Our laboratory studies the involvement of the glutamatergic system in the aggressiveness of glioma, and some ligands of glutamate receptors cannot permeate the BBB. Here, glioma-implanted rats were treated by a technique that delivers ligands directly into the cerebrospinal fluid by puncture into the cisterna cerebellomedullaris. Rats were anesthetized and fixed in a rodent stereotactic device. The head was gently tilted downwards at an angle that allowed exposure of the cisterna. Injection into the cisterna was done freehand using a gingival needle coupled to a microsyringe. The efficiency of intracisternal injection was demonstrated using a methylene blue solution. This type of injection is adaptable for any rodent model using small volumes of a variety of other drugs, and is an interesting method for neuroscience studies.

Keywords

Neurobiology Neuroscience Drug administration Intracisternal injection Cisterna magna Cerebrospinal fluid treatment Central nervous system Surgical technique Rodent 

Notes

Acknowledgements

This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) – Edital Doenças Neurodegenerativas, Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), and Financiadora de Estados e Projetos (FINEP).

Compliance with Ethical Standards

Conflict of interest

All authors claim that there are no conflicts of interest.

References

  1. 1.
    Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: An overview: structure, regulation, and clinical implications. Neurobiol Dis 2004, 16: 1–13.CrossRefPubMedGoogle Scholar
  2. 2.
    Pardridge WM. Drug transport in brain via the cerebrospinal fluid. Fluids Barriers CNS 2011, 8: 7.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Niswender CM, Conn PJ. Metabotropic glutamate receptors: Physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 2010, 50: 295–322.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Pereira MS, Klamt F, Thomé CC, Worm PV, de Oliveira DL. Metabotropic glutamate receptors as a new therapeutic target for malignant gliomas. Oncotarget 2017, 8: 22279–22298.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Flor PJ, Battaglia G, Nicoletti F, Gasparini F, Bruno V. Neuroprotective activity of metabotropic glutamate receptor ligands. Adv Exp Med Biol 2002, 513: 197–223.CrossRefPubMedGoogle Scholar
  6. 6.
    DeVos SL, Miller TM. Direct intraventricular delivery of drugs to the rodent central nervous system. J Vis Exp 2013: e50326.Google Scholar
  7. 7.
    Serrats J, Schiltz JC, García-Bueno B, van Rooijen N, Reyes TM, Sawchenko PE. Dual roles for perivascular macrophages in immune-to-brain signaling. Neuron 2010, 65: 94–106.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Newman TA, Galea I, van Rooijen N, Perry VH. Blood-derived dendritic cells in an acute brain injury. J Neuroimmunol 2005, 166: 167–172.CrossRefPubMedGoogle Scholar
  9. 9.
    Drabek T, Janata A, Jackson EK, End B, Stezoski J, Vagni VA, et al. Microglial depletion using intrahippocampal injection of liposome-encapsulated clodronate in prolonged hypothermic cardiac arrest in rats. Resuscitation 2012, 83: 517–526.CrossRefPubMedGoogle Scholar
  10. 10.
    Wang XF, Zhao TY, Su RB, Wu N, Li J. Agmatine prevents adaptation of the hippocampal glutamate system in chronic morphine-treated rats. Neurosci Bull 2016, 32: 523–530.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Wang Z, Liang S, Yu S, Xie T, Wang B, Wang J, et al. Distinct roles of dopamine receptors in the lateral thalamus in a rat model of decisional impulsivity. Neurosci Bull 2017, 33: 413–422.CrossRefPubMedGoogle Scholar
  12. 12.
    Chen Y, Imai H, Ito A, Saito N. Novel modified method for injection into the cerebrospinal fluid via the cerebellomedullary cistern in mice. Acta Neurobiol Exp (Wars) 2013, 73: 304–311.Google Scholar
  13. 13.
    de Groot J, Sontheimer H. Glutamate and the biology of gliomas. Glia 2011, 59: 1181–1189.CrossRefPubMedGoogle Scholar
  14. 14.
    Willard SS, Koochekpour S. Glutamate signaling in benign and malignant disorders: Current status, future perspectives, and therapeutic implications. Int J Biol Sci 2013, 9: 728–742.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Mahat MY, Fakrudeen Ali Ahamed N, Chandrasekaran S, Rajagopal S, Narayanan S, Surendran N. An improved method of transcutaneous cisterna magna puncture for cerebrospinal fluid sampling in rats. J Neurosci Methods 2012, 211: 272–279.CrossRefPubMedGoogle Scholar
  16. 16.
    Liu L, Duff K. A technique for serial collection of cerebrospinal fluid from the cisterna magna in mouse. J Vis Exp 2008. pii: 960.  https://doi.org/10.3791/960.
  17. 17.
    Liu CH, D’Arceuil HE, de Crespigny AJ. Direct CSF injection of MnCl(2) for dynamic manganese-enhanced MRI. Magn Reson Med 2004, 51: 978–987.CrossRefPubMedGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Thainá Garbino dos Santos
    • 1
  • Mery Stéfani Leivas Pereira
    • 1
  • Diogo Losch Oliveira
    • 1
  1. 1.Laboratory of Cellular Neurochemistry, Departamento de Bioquímica, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil

Personalised recommendations