Literature DB >> 20153340

Pharmacokinetics and bioactivity of glial cell line-derived factor (GDNF) and neurturin (NTN) infused into the rat brain.

Piotr Hadaczek1, Louisa Johnston, John Forsayeth, Krystof S Bankiewicz.   

Abstract

Convection-enhanced delivery (CED) of GDNF and NTN was employed to determine the tissue clearance of these factors from the rat striatum and the response of the dopaminergic system to a single infusion. Two doses of GDNF (15 and 3 microg) and NTN (10 microg and 2 microg) were infused into the rat striatum. Animals were euthanized 3, 7, 14, 21, and 28 days post-infusion. Brains were processed for ELISA, HPLC, and immunohistochemistry (IHC). Both doses of the infused GDNF resulted in a sharp increase in striatal GDNF levels followed by a rapid decrease between day 3 and 7. Interestingly, IHC revealed GDNF in the septum and the base of the brain 14 days after GDNF administration. Dopamine (DA) turnover was significantly increased in a dose-dependent manner for more than 7 days after a single GDNF infusion. NTN persisted in the brain for at least two weeks longer than GDNF. It also had more persistent effects on DA turnover, probably due to its precipitation in the brain at neutral pH after infusion. Our data suggest that daily or continuous dosing may not be necessary for delivering growth factors into the CNS. (c) 2010 Elsevier Ltd. All rights reserved.

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Year:  2010        PMID: 20153340      PMCID: PMC2849906          DOI: 10.1016/j.neuropharm.2010.02.002

Source DB:  PubMed          Journal:  Neuropharmacology        ISSN: 0028-3908            Impact factor:   5.250


  39 in total

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