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  • The efficacy of 6-OHDA Stereotaxic Neurosurgical Model Compared to Haloperidol Pharmacological Model - Two Parkinson´s Disease Animal Models.

    Final Number:
    1478

    Authors:
    Junia Vieira dos Santos; Rafaela Carneiro Cordeiro; Luciana Dias Belchior; Marcos Romário Matos de Sousa; Gersilene Valente de Oliveira; Aline Monte Santos; Camila Medeiros Dantas; Danielle Silveira Macêdo

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2012 Annual Meeting

    Introduction: Parkinson´s disease (PD) is a disabling neurodegenerative disorder, which pathophysiological pathway could be reproduced by neurotoxin-based models, as 6-OHDA rat model. Animal models are essential steps to validate the efficacy of new therapeutic procedures in PD. The present study aims to evaluate the effectiveness of pharmacological model of induced parkinsonism compared to the surgical method of induced dopaminergic degeneration.

    Methods: In conducting this study, 16 Wistar rats (250-300g) were divided into two groups containing eight animals per group: the group treated with haloperidol (GH) and surgical group (CG). During 21 days, Haloperidol 1% (10mg/kg animal, i.p) was administered to the animals of group GH. CG group animals underwent stereotaxic surgery degeneration-induced by infusion of 6-hydroxydopamine (6mg/mL) solution in 0.02% ascorbic acid in the right striatum (RS). Ketamine (50mg/mL) and xylazine (20mg/ml) were used to anesthesia induction. The infusion rate of 6-OHDA was equivalent to 0.2 g / min for 5 minutes. After 24 hours of the surgical procedure ending, saline administration (i.p) started. On day 21, all animals were sacrificed and then the hippocampus (HC) and RS were dissected and used in the preparation of homogenates with phosphoric acid (150mM). For determination of lipid peroxidation, levels of thiobarbituric acid reactive species were measured in brain areas. Lipid peroxidation was determined by the absorbance at 532 nm and expressed as mmol of malondialdehyde (MDA)/g tissue. Statistical analysis was based on the ANOVA test.

    Results: There was significant variation (P <0.01) at MDA content in samples of HC of the two groups. Significant variation (P> 0.05) wasn´t observed at MDA content in RS and the GSH concentrations of HC and RS.

    Conclusions: Although both models promote the degeneration of nigroestriatais neurons, the stereotactic surgery model-based induces increased oxidative stress in the hippocampal region, possibly contributing to the atrophy of this region consistent with the dementia observed in Parkinson's disease.

    Patient Care: Determining a more feasible model for Parkinson´s disease is essential to study the PD´s pathophysiology and to evaluate the efficacy of new pharmacotherapies.

    Learning Objectives: 1-) Identify what model was more effective to reproduce PD; 2-) Understand the importance of animal models to validate new therapies.

    References:

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