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Method for establishing non-human primate animal model of parkinson disease by lateral ventricle administration of MPP<+>

A Parkinson's disease, animal model technology, applied in the field of biomedicine, can solve problems such as difficult MPP, and achieve the effects of typical behavioral symptoms, good basic physiological conditions, and easy operation

Inactive Publication Date: 2013-10-09
KUNMING INST OF ZOOLOGY CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to MPP + It cannot pass through the blood-brain barrier, so it is difficult for traditional drug delivery methods to MPP + into the central nervous system

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0011] Example 1: Rhesus monkeys are male, 7 years old. MPP + Purchased from Sigma, USA.

[0012] The stainless steel catheter in the lateral ventricle delivery device has an inner diameter of 0.5 mm and a length of 35 mm. The length of the stainless steel dosing tube is 35.5mm.

[0013] The localization coordinates of the lateral ventricle were obtained from monkey brain atlas and MRI data. The positioning coordinates of the lateral ventricle are: 1mm anterior to AP0, 9.6mm lateral, and 22-26mm below the skull. When positioning according to the above coordinates, if clear cerebrospinal fluid continuously gushes out from the orifice after the catheter is inserted into the brain to a certain depth, it can be known that the end of the catheter has entered the lateral ventricle. Then the catheter was fixed with dental tray cement and skull titanium screws, and the mouth of the catheter was blocked with a stainless steel plug. After the animal recovered for 8 days, the drug wa...

Embodiment 2

[0015] Example 2: Cynomolgus monkeys are male, 7 years old. The positioning coordinates of the lateral ventricle in cynomolgus monkeys are: 21-25mm anterior to AP0, 1.2-1.8mm lateral, and 15-20mm below the skull. When positioning according to the above coordinates, if clear cerebrospinal fluid continuously gushes out from the orifice after the catheter is inserted into the brain to a certain depth, it can be known that the end of the catheter has entered the lateral ventricle. Then fix the catheter with dental tray cement and skull titanium screws, and plug the mouth of the catheter with a stainless steel plug. After a week of recovery, the drug administration is started. Every time the drug is administered, the plug is pulled out, the drug tube is inserted, and the MPP is inserted. + Saline solution is injected into the lateral ventricle through a syringe attached to the end of the administration tube, MPP + The concentration is 0.7mg / mL, each administration is 0.25mL, after...

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Abstract

A method for establishing a non-human primate animal model of parkinson disease by lateral ventricle administration of MPP<+> belongs to the biomedical technology. The method comprises the following steps: 1, preparing a lateral ventricle administration device; 2, according to a monkey brain atlas and nuclear magnetic resonance imaging data, acquiring a positioning coordinate of a lateral ventricle; 3, inserting a catheter into a lateral ventricle administration position through a monkey stereotaxic instrument, and beginning to administrate the drug after 5-8 days after the animal recovers; injecting a physiological saline solution containing MPP<+> into the lateral ventricle by an injector connected with the tail end of an administration pipe, with the MPP<+> concentration of 0.5-0.7 mg / mL and each administration dosage of 0.1-0.3 mL; carrying out administration one time every 48-72 hours, and after administration for 30-60 days, establishing the non-human primate animal model of the parkinson disease. The method employs a new administration mode that the MPP<+> (1-methyl-4-phenylpyridinium iodide) drug is directly injected into the lateral ventricle of the animal for modeling. With lateral ventricle injection, MPP<+> can perform whole brain circulation together with cerebrospinal fluid to specifically damage dopamine neurons in a brain and cause symptoms of the parkinson disease, and can furthest avoid toxic and side effects of the drug on a periphery.

Description

technical field [0001] The invention belongs to biomedical technology, and in particular relates to a method for establishing an animal model. Background technique [0002] For many years, non-human primates (such as macaques, crab-eating monkeys, etc.) have been ideal objects for establishing animal models of Parkinson's disease. The commonly used modeling methods mainly use MPTP (1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine) intravenous infusion, intramuscular injection or carotid artery one-time administration to establish animal models of chronic or acute Parkinson's disease. Although these methods can induce typical behavioral symptoms of Parkinson's disease, there are obvious disadvantages. A review of animal models of Parkinson's published by M. Gerlach and P. Riederer concluded the following points: Animals during the modeling period showed large individual differences, animals were subject to drug-induced toxic side effects, and behavioral symptoms Unstable, with...

Claims

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Application Information

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IPC IPC(8): A61K31/44
Inventor 李浩雷小光胡新天张宝荣
Owner KUNMING INST OF ZOOLOGY CHINESE ACAD OF SCI
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