Time course of brain oxidative damage caused by intrastriatal administration of 6-hydroxydopamine in a rat model of Parkinson’s disease

Abstract

The unilateral and intrastriatal injection of 6-hydroxydopamine is commonly used to provide a partial lesion model of Parkinson’s disease in the investigation of the molecular mechanisms involved in its pathogenesis and to assess new neuroprotective treatments. Its capacity to induce neurodegeneration has been related to its ability to undergo autoxidation in the presence of oxygen and consequently to generate oxidative stress. The aim of the present study was to investigate the time course of brain oxidative damage induced by 6-hydroxydopamine (6 μg in 5 μl of sterile saline containing 0.2% ascorbic acid) injection in the right striatum of the rat. The results of this study show that the indices of both lipid peroxidation (TBARS) and protein oxidation (carbonyl and free thiol contents) increase simultaneously in the ipsilateral striatum and ventral midbrain, reaching a peak value at 48-h post-injection for both TBARS and protein carbonyl content, and at 24 h for protein free thiol content. A lower but significant increase was also observed in the contralateral side (striatum and ventral midbrain). The indices of oxidative stress returned to values close to those found in controls at 7-day post-injection. These data show that the oxidative stress is a possible triggering factor for the neurodegenerative process and the retrograde neurodegeneration observed after 1-week post-injection is a consequence of the cell damage caused during the first days post-injection. The optimal time to assess brain indices of oxidative stress in this model is 48-h post-injection.