Experimental Study On Protecting Nigral Dopamine Neurons By Kynurenic Acid

Since for one century past, the treatment of Parkinson' disease was primarily aimed at its symptom. In the recent thirty years, with the development of pathophysiologic research, it is well known that the dopamine content in PD patient's nigral striatum system is lower than normal, so L-DOPA has been used as substitutive therapy. Up to now L-DOPA has still been the most efficacious drug. But after a long following-up it is found that a majority of patients are suffering from symptom fluctuation and akinesia, which are hard to manage. It is more terrible that the disease-process is increasingly aggravate. The protection of DA neurons have gradually become the second innovation of PD cure.Pathogenic factors of PD are related to oxidizing reaction, energy metabolism disorder and EAA neurotoxicity. The protective treatment measures involves following aspects: monoamine oxidase-B inhibitor, DA receptor exitomotor, iron chelating agent, other anti-oxidant, medicine improving energy metabolism and EAA receptor agonist.KYNA is a broad-spectrum agonist of Glu receptor which may protect DA neurons from Glu neurotoxicity.Objective: To verify and evaluate the protective function of K YNA on the SN dopamine cell bodies and fibres, which is used prior to 6-OHDA as the broad-spectrum antagonist on glutamaternic receptors.Methods: A total 60 adult female SD rats in 4 groups (each of the 4 groups consisting of 10 rats). Group 1,2,3,4 received, respectively, a unilateral microinjection of normal saline, KYNA, KYNA+6-OHDA or 6-OHDA, into the left ventral tegmental area(VTA) and SNc. In three days , the changes of tyrosine hydroxylase-like neurons in SNc and dopamine fiber in VTA were investigated in immunocytochemical methods. Data were reported as mean 盨D. Statistical significance levels were calculated by using Analysis of Variance and Rank test.Results: In the third day after injection, the ethologic observation was performed in motivation by apomorphine. Group A and B have no symptom. Group C was significantly improved than group D. The number of tyrosine hydroxylase immunoreactive cells in SNc on the injection side of 4 groups were 577?0.89, 551.3?6.11, 434.4?4.69, 189.4?6.66/slicexlO/perspeciemen.The number of TH-positive cellsin groups 1,2,3 significantly increase in comparison with the group 4 (P<0.01). Application of KYNA prior to 6-OHDA produced a significant increase of TH-positive fibers than group D around the injection sites in VTA.Conclusion .These data indicate that the early application of Glu receptor antagonist KYNA may decrease neurotoxic damage of 6-OHDA on nigral DA neurons. It is clinically likely to retard and block DA neurons from increasing death in PD. This method is more important to the early-phase PD patients, which is considered as the second innovation of PD treatment.