Advertisement

Intracerebral Infusion of Neurotrophic Factors

  • Theo Hagg
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 399)

Abstract

Neurotrophic factors are among the most potent neuroprotective and neuroregenerative agents known. However, they cross the adult mammalian blood-brain barrier very poorly and can have serious peripheral side effects. These problems can be solved by using chronic infusions with small pumps to directly deliver known quantities of these proteins into selected regions of the brains of small experimental animals such as rats and mice. The method consists of commercially available Alzet osmotic pumps that are placed under the skin and are connected to commercially available metal infusion cannulas whose tip can be stereotactically placed in virtually any location of the brain. Different models of pumps that fit comfortably in rodents can be selected for infusion between 1 and 28 days and at infusion rates ranging between 8 and 0.25µL/h, respectively. Methodological details are provided for the successful use of proteins and to minimize the time of the surgery.

Key Words

Alzet central nervous system chronic infusion degeneration; growth factor mouse intraventricular pharmacological rat regeneration 

References

  1. 1.
    Hagg, T., Manthorpe, M., Vahlsing, H. L., and Varon, S. (1988) Delayed treatment with nerve growth factor reverses the apparent loss of cholinergic neurons after acute brain damage. Exp. Neurol. 101, 303–312.CrossRefPubMedGoogle Scholar
  2. 2.
    Oudega, M. and Hagg, T. (1996) Nerve growth factor promotes regeneration of sensory axons into adult rat spinal cord. Exp. Neurol. 140, 218–229.CrossRefPubMedGoogle Scholar
  3. 3.
    Lu, X., Maysinger, D., and Hagg, T. (2002) Tyrosine phosphatase inhibition enhances neurotrophin potency and rescues nigrostriatal neurons in adult rats. Exp. Neurol. 178, 259–267.CrossRefPubMedGoogle Scholar
  4. 4.
    Sofroniew, M. V., Howe, C. L., and Mobley, W. C. (2001) Nerve growth factor signaling, neuroprotection, and neural repair. Annu. Rev. Neurosci. 24, 1217–1281.CrossRefPubMedGoogle Scholar
  5. 5.
    Thoenen, H. and Sendtner, M. (2002) Neurotrophins: from enthusiastic expectations through sobering experiences to rational therapeutic approaches. Nat. Neurosci. 5 Suppl, 1046–1050.CrossRefPubMedGoogle Scholar
  6. 6.
    Liu, X. and Chen, C. (2005) Strategies to optimize brain penetration in drug discovery. Curr. Opin. Drug Discov. Dev. 8, 505–512.Google Scholar
  7. 7.
    Wu, D. (2005) Neuroprotection in experimental stroke with targeted neurotrophins. NeuroRx 2, 120–128.CrossRefPubMedGoogle Scholar
  8. 8.
    Hagg, T. (1994) Continuous central nervous system infusion with Alzet osmotic pumps, in Methods in Neurosciences, Vol. 21: Providing Pharmacological Access to the Brain: Alternate Approaches (Flanagan T., Emerich D., and Winn S., eds.), Academic Press, San Diego, CA, pp. 201–213.Google Scholar
  9. 9.
    Paxinos, G. and Watson, C. (2005) The Rat Brain in Stereotaxic Coordinates, The New Coronal Set. 5 ed., Academic Press, San Diego, CA.Google Scholar
  10. 10.
    Paxinos, G. and Franklin, K. (2002) The Mouse Brain in Stereotaxic Coordinates. 2 ed., Academic Press, San Diego, CAGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Theo Hagg
    • 1
  1. 1.Kentucky Spinal Cord Injury Research Center, Department of Neurological Surgery and Department of Pharmacology and ToxicologyUniversity of LouisvilleLouisville

Personalised recommendations