Single administration of GDNF into the striatum induced protection and repair of the nigrostriatal dopaminergic system in the intrastriatal 6-hydroxydopamine injection model of hemiparkinsonism

Purpose: Neurotrophic factor delivery into the brain is a promising approac h in the treatment of Parkinson's disease. Glial cell line-derived neurotro phic factor (GDNF) is one of the most potent neurotrophic factors for dopam inergic neurons. Although multiple injections of GDNF into the brain are co mmonly performed in experimental studies, the present study investigates th e efficacy of using a single injection of GDNF, which may be useful in clin ically applying this treatment. Methods: Unilateral 6-hydroxydopamine (6-OHDA) administration into the stri atum was performed in Sprague-Dawley rats to create a partial lesion of the nigrostriatal DA system. These parkinsonian model rats received a single i njection of human recombinant GDNF into the same portion of the striatum ei ther 24 h before or 4 weeks after 6-OHDA treatment. Results: GDNF injected into the striatum before 6-OHDA administration poten tly protected the dopaminergic system, as shown by the numbers of mesenceph alic dopaminergic neuron cell bodies and dopaminergic nerve terminal densit ies in the striatum. Dopaminergic neuron cell bodies and fiber densities we re also significantly restored when GDNF was given after 6-OHDA administrat ion, although the degree of restoration was lower than in the protective ex periment. GDNF administration ameliorated apomorphine-induced rotational be havior in animals receiving it either before or after 6-OHDA treatment. How ever, the degree of improvement was less prominent when GDNF was injected a fter 6-OHDA. Conclusion: Intracerebral GDNF administration exerts both protective and re generative effects on the nigrostriatal dopaminergic system, a finding whic h may have implications for the development of new treatment strategies for Parkinson's disease.