title: Long-term neuroprotection and neurorestoration by glial cell-derived neurotrophic factor microspheres for the treatment of Parkinson's disease.
abstract: BACKGROUND
  Glial cell-derived neurotrophic factor is a survival factor for dopaminergic neurons and a promising candidate for the treatment of Parkinson's disease. However, the delivery issue of the protein to the brain still remains unsolved. Our aim was to investigate the effect of long-term delivery of encapsulated glial cell-derived neurotrophic factor within microspheres.
  
  
  METHODS
  A single dose of microspheres containing 2.5 μg of glial cell-derived neurotrophic factor was implanted intrastriatally in animals 2 weeks after a 6-hydroxydopamine lesion.
  
  
  RESULTS
  The amphetamine test showed a complete behavioral recovery after 16 weeks of treatment, which was maintained until the end of the study (week 30). This effect was accompanied by an increase in dopaminergic striatal terminals and neuroprotection of dopaminergic neurons.
  
  
  CONCLUSIONS
  The main achievement was the long-term neurorestoration in parkinsonian animals induced by encapsulated glial cell-derived neurotrophic factor, suggesting that microspheres may be considered as a means to deliver glial cell-derived neurotrophic factor for Parkinson's disease treatment.
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, Pamplona, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Garbayo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ansorena
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Lanciego
authors.forename: María Jose
authors.initials: MJ
authors.lastname: Blanco-Prieto
authors.forename: María S
authors.initials: MS
authors.lastname: Aymerich
mesh_terms: D020341:Absorbable Implants; D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality; D051098:Glial Cell Line-Derived Neurotrophic Factors / Q000008:administration & dosage*; D008863:Microspheres; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase
chemical_list: D018663:Adrenergic Agents; D051098:Glial Cell Line-Derived Neurotrophic Factors; D018696:Neuroprotective Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase