Neuroprotection of nerve growth factor-loaded microspheres on the D2 dopaminergic receptor positive-striatal neurones in quinolinic acid-lesioned rats: a quantitative autoradiographic assessment with iodobenzamide

Huntington's disease (HD) results from the degeneration of striatal neurone s, mainly gamma-aminobutyric acid (GABA)ergic projection neurones and latel y cholinergic interneurones. The use of trophic factors as agents able to p revent such neural degeneration is a promising strategy. The aim of this st udy was to validate nerve growth factor-loaded (NGF-loaded) poly-D,L-lactid e-co-glycolide (PLGA) microspheres for treatment of HD in a rat model with quinolinic acid lesion using autoradiographic study of D2 dopaminergic rece ptors (D2R). This target is expressed by about half of striatal neurones an d its scintigraphic exploration has already been performed for the follow-u p of this degenerative process. Ex vivo autoradiography of D2R performed wi th iodobenzamide, the widely used ligand for single photo emission computer ized tomography, reveal ed slight neuroprotection. Moreover, tolerance of m icrospheres was demonstrated by in vitro autoradiography with the marker of gliosis, [H-3]-PK 11195. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.