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Pharmaceutical composition for promoting axon regeneration after spinal cord damage and behavior function recovery

A technology of axon regeneration and composition, applied in the field included in the present invention, can solve problems such as clinical trials of rare spinal cord injury cases

Inactive Publication Date: 2009-04-15
郑宏志
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, ChABC has rarely been used in clinical trials in spinal cord injury cases due to its toxicity

Method used

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  • Pharmaceutical composition for promoting axon regeneration after spinal cord damage and behavior function recovery
  • Pharmaceutical composition for promoting axon regeneration after spinal cord damage and behavior function recovery
  • Pharmaceutical composition for promoting axon regeneration after spinal cord damage and behavior function recovery

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Insertion of catheter and infusion of chondroitinase ABC after T8 complete spinal cord transection

[0032] Female Sprague-Dawley (SD) rats (each weighing 250 to 300 g) were used in this experiment. All surgical procedures were performed under inhalational anesthesia with isoflurane and body temperature maintained at approximately 37°C on a homoeothermic blanket. The skin over the foramina was harvested and a longitudinal midline incision was made to expose the capitate and layer C1. The epidural space is established just above the C1 level, and the catheterization reaches the T8-T9 level. Wounds were closed layer by layer, and surfaced catheters were used to infuse chondroitinase ABC.

[0033] One week after cannulation and confirmation of normal hindlimb movement, the animals underwent a T8 gross laminectomy at the T8 level for exposure of the spinal cord and cannulation. A complete spinal cord transection was performed with the two stumps held up in a m...

Embodiment 2

[0035] Example 2: Evaluation of Behavioral Function

[0036]Weekly after surgery, all animals underwent behavioral function assays for 8 weeks. All behavioral function measurements were videotaped, and the two examiners participating in the behavioral function evaluation were blinded to each group. Rat hindlimb locomotor's behavioral function was evaluated by the Basso, Beattie, Bresnahan (BBB) ​​open (photo) field assay. Each evaluation session lasts 5 minutes. The open (photographed) field locomotor's activity score was determined from 0 to 21 (0 being no movement, 21 being normal movement) by observation and scoring of behavioral functions including trunk, tail and hind limbs.

[0037] refer to figure 1 , after surgery and ChABC treatment, between ChABC 1U / ml group (T8 tx+chABC 1U), ChABC 5U / ml group (T8tx+chABC 5U) and control group (T8 tx+saline, only T8tx+tube and only T8tx) There were statistical differences in the locomotor's functional evaluation of the...

Embodiment 3

[0038] Example 3: Anterograde labeling of axons passing through the transection site

[0039] Eight weeks later, female SD rats were anesthetized under isoflurane inhalation. The spinal cord was exposed at T10 level, and 4% WGA-HRP was injected into the motor cortex of the brain via a micro-syringe. Three sites were injected by a slow pump system (disperse injection on 0.24 μl x 3 on each side). Two days after microinjection, the animals were sacrificed under anesthesia by carotid infusion of 4% paraformaldehyde. Spinal cords and brainstems were removed, post-fixed and cryopreserved in 30% sucrose overnight for serial sectioning. The spinal cord was sectioned longitudinally and the brainstem was sectioned coronally at a thickness of 30 μm.

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Abstract

The invention provides a pharmaceutical composition for promoting the regeneration of axons and the recovery of behavioral functions of examinees who suffer neurologic damage. The pharmaceutical composition contains chondroitinase ABC (ChABC) with safe and effective amount and a pharmaceutically accepted carrier. The invention also provides application of the ChABC in preparation of the pharmaceutical composition for promoting the regeneration of the axons and the recovery of the behavioral functions of the examinees, wherein the pharmaceutical composition contains the ChABC with the safe and effective amount which is used for promoting the regeneration of the axons and the recovery of the behavioral functions of the examinees who suffer neurologic damage. The pharmaceutical composition contains about 0.1 to 10U / ml of ChABC, wherein the pharmaceutical composition is infused to injured parts. After being used, the ChABC of the pharmaceutical composition has obvious function of improving the regeneration, and outstanding recovery effect on the behavioral functions.

Description

Background of the invention [0001] The present invention relates to a method and pharmaceutical composition for promoting axonal regrowth and behavior recovery in spinal cord injury. [0002] In mammals, adult neural tissue has limited regenerative capacity. Consequently, many brain or spinal cord lesions fail to repair or reestablish functional connectivity autogenously. Many complex causes, including immune response molecules and suppressors affect the regenerative capacity of the adult central nervous system. After spinal cord injury (SCI), chondroitin sulfate proteoglycans (CSPGs) are upregulated by astrocytes and oligodendrocytes at the injury site to limit axon regeneration. [0003] While some reports have shown that CSPG expression is often upregulated after injury, recent studies have focused on changes in the expression of individual family components following different methods of injury. CSPGs consist of glycosaminoglycan (GAG), a key limiting factor that blocks...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/48A61P25/00
Inventor 黄文成郭玟君郑宏志
Owner 郑宏志
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