Categories

1.        PD Model - MPTP-induced hemi-parkinsonian monkey

2.        PD Model - MPTP-induced whole body parkinsonian monkey

3.      PD Model - 6-OHDA induced hemi-parkinsonian rat

PD - MPTP-induced hemi-parkinsonian monkey model

- Adult rhesus monkeys, body weight 7-10kg, male or female.

- Single injection of MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine) via unilateral carotid artery induced hemi-parkinsonian model

-  Parkinsonian syndrome was observed in one side of the body: forearm tremor, bradykinesia, posture curve. We have special equipments to test and record monkey model’s behavior.

-  The behaviors and motor movements of each monkey will be scored and rated individually according to an established scale described by Gash, et al. (Nature 1996; 380:252-5).  Prior to the study, the trained observers will reliably score the same categories with a Pearson correlation coefficient of >0.90.

- Biochemistry evaluations including TH enzyme assay,

-  HPLC analysis of dopamine, HVA, DOPAC, 5-HT and 5-HIAA in the brain or in CSF.

- Immunohistochemistry analysis to show the dopaminergic neurons loss in the substatia nigra of lesioned side (indicated by arrow in the fig below).                        

-  Electron microscopic analysis to intensify the histochemistry reaction and improve visualization of immunostained brain structures.

PD - MPTP-induced whole body parkinsonian monkey

-  One method is multiple intravenous injection of MPTP at 0.2-0.5mg/kg，iv, once a day for 15-18 days until parkinsonian syndrome appeared.  

- Another method is a two-stage lesion approach in which MPTP was administered via the carotid arteries. The first infusion through one artery produced a hemiparkinsonian state and was followed several months later by a second MPTP infusion into the contralateral carotid artery to induce bilateral parkinsonism (Smith et al. Neuroscience 1993; 52:7-16 ).

- Animals receiving lesions were evaluated using a battery of tests which included a monkey parkinsonism rating scale, a movement time-task and continuous monitoring of home cage activity. All animals monitored showed significant decreases in activity levels of up to 95% following the second lesion. These decreased activity levels remained stable throughout the observation period of up to 12 months post-lesion.

-  In addition to the decreased home cage activity, bilaterally lesioned animals displayed bilateral parkinsonian features including akinesia, bradykinesia, rigidity, tremor and balance and gait disturbances which were stable, following an acute period of up to 45 days, for the remainder of the study.

- Treated animals display the cardinal features of parkinsonism and respond appropriately to the standard antiparkinsonian drug, levodopa.

PD - 6-OHDA induced hemi-parkinsonian rat model

- Adult SD rats, male or female

- Unilateral nigrostriatal lesion is produced by the stereotaxic micro-injection of 6-OHDA into the right ascending meso-striatal DA fiber bundle.

- Motor asymmetry is assessed by measuring rotational behavior as follows:

Amphetamine-induced rotation

Apomorphine-induced rotation

- Biochemistry assays for TH enzyme level, HPLC analysis of CSF sample or brain sample for level of dopamine, HVA, DOPAC, 5-HT and 5-HIAA.

-  Immunohistochemistry for evaluating brain morphology changes

-  Intracerebral micro-dialysis for measuring levels of catecholamines in the brain in life animals.