Prevention of neurotoxin damage of 6-OHDA to dopaminergic nigral neuron by subthalamic nucleus lesions

Object: To investigate the possibility that subthalamic nucleus (STN) ablation could prevent the toxicity of the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). Methods: Sixty rats were divided into 6 groups (n = 10). The control group received a unilateral microinjection of 6-OHDA into the right ventral tegmental area (VTA) and the right median forebrain bundle (MFB). Group 1 received an administration of kainic acid (KA) into the right STN and, 1-week later, an injection of 6-OHDA in the right VTA and MFB. Groups 2-5 received an injection of 6-OHDA in the right VTA and MFB, 1 h, 2 h, 3 days, and 7 days before KA in the right STN respectively. Four weeks later, the changes of tyrosine hydroxylase (TH)-positive (dopaminergic) neurons in the SNc were investigated with immunocytochemical and morphometrical methods. Results: The number of TH-positive cells in the SNc on the injected side of treated groups (groups 1-5) and control group were 71.46 +/- 6.84, 57.07 +/- 5.54, 51.09 +/- 4.85, 12.68 +/- 2.67, 4.15 +/- 1.60 and 3.40 +/- 1.54/slice, which decreased to 96.7, 72.9, 69.8, 17.2, 5.6 and 4.4% of the non-injected side, respectively. The number of TH-positive neurons in groups 1-4 significantly increased in comparison with the controls (p < 0.05, 0.01). In group 5, there were no remarkable differences in contrast to the number of TH-positive neurons of the controls (p > 0.05). The difference in the number of TH-positive neurons between groups 1-5 was statistically significant (p < 0.01). Conclusion: The results indicate that STN ablation can provide antiglutamate-based neuroprotection of the dopaminergic nigrostriatal pathway against 6-OHDA toxicity. Copyright (C) 2001 S. Karger AG, Basel.