当前位置： SCI文献检索 > EXPERIMENTAL NEUROLOGY期刊下所有文献 > Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin.

Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin.

Abstract：

:Convection-enhanced delivery (CED) distributes macromolecules in the brain in a homogeneous, targeted fashion in clinically useful volumes. However, the binding of growth factors to heparin-binding sites in the extracellular matrix may limit the volume of distribution (V(d)). To overcome this limitation, we examined the effects of heparin coinfusion on V(d) of glial-derived neurotrophic factor (GDNF), neurturin (NTN), artemin, and a nonspecifically bound protein, albumin. Heparin coinfusion significantly enhanced the V(d) of GDNF and GDNF-homologous trophic factors, probably by binding and blocking heparin-binding sites in the extracellular matrix. Furthermore, coinfusion of heparin with NTN enhanced striatal dopamine metabolism, compared to trophic factor administered alone. The negligible benefit of GDNF in recent clinical trials of Parkinson's disease may result from limited tissue distribution. Heparin coinfusion during CED targeting the striatum may alleviate this important limitation. This study demonstrates the influence of receptor binding on the distribution of trophic factors in the CNS.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Hamilton JF,Morrison PF,Chen MY,Harvey-White J,Pernaute RS,Phillips H,Oldfield E,Bankiewicz KS

doi

10.1006/exnr.2000.7571

keywords:

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

155-61

issue

1

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(00)97571-X

journal_volume

168

pub_type

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