Applications of receptor antagonist in treating focal cerebral ischemia injuries

A technology for focal cerebral ischemia and antagonists, applied in the field of biomedicine, can solve the problem of no disclosure, and achieve the effects of reducing cerebral edema, improving neurological function, and reducing infarct volume

Inactive Publication Date: 2015-07-29
ZHEJIANG ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

CysLT 2 R mediates OGD-induced microglial activation and neuronal injury in mixed cultures of cortical cells, indicating that neuronal injury is closely related to microglial activation, but HAMI 3379 has no effect on focal cerebral ischemia in rats at the global level Whether the injury has a protective effect, the prior art does not disclose any

Method used

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  • Applications of receptor antagonist in treating focal cerebral ischemia injuries
  • Applications of receptor antagonist in treating focal cerebral ischemia injuries
  • Applications of receptor antagonist in treating focal cerebral ischemia injuries

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0140] Example 1, CysLT 2 The protective effect of intracerebroventricular administration of R selective antagonist HAMI 3379 on acute injury of focal cerebral ischemia in rats

[0141] 1. Behavioral changes

[0142] After cerebral ischemia in rats, symptoms of neurological deficits and sensorimotor deficits (reduced inclination angle of the inclined plate) appeared. A single dose of HAMI 3379 (10, 100ng, i.c.v.) and Promilast (0.1 mg / kg, i.p.) 30 minutes before surgery can significantly reduce neurological symptoms ( figure 1 A), increase the slope angle of the inclined plate ( figure 1 B). HAMI 3379 (1ng, i.c.v.) had no significant effect. The results indicated that intracerebroventricular injection of HAMI 3379 could dose-dependently improve the neurological impairment in rats after cerebral ischemia.

[0143] 2. Cerebral infarct volume

[0144] After focal cerebral ischemia-reperfusion injury in rats, gross observation of the whole brain shows that the hemisph...

Embodiment 2

[0152] Example 2, CysLT 2 Protective effect of intraperitoneal injection of R-selective antagonist HAMI 3379 on focal cerebral ischemic acute injury and inflammation in rats

[0153] 1. Behavioral changes

[0154] After cerebral ischemia in rats, symptoms of neurological deficits and sensorimotor deficits (reduced inclination angle of the inclined plate) appeared. Administration of HAMI 3379 (0.1, 0.2, 0.4 mg / kg, i.p.) and promilast (0.1 mg / kg, i.p.) 30 minutes before operation and immediately after ischemia-reperfusion can significantly reduce the neurological deficit of ischemia-reperfusion for 24 hours. Symptom score ( Figure 6 D), increase the angle of inclination of the inclined plate ( Figure 6 E). HAMI 33790.025, 0.05mg / kg dose group has no obvious effect, the results show that intraperitoneal injection of HAMI 3379 can dose-dependently improve the neurological damage in rats after cerebral ischemia. A single administration of HAMI 3379 (0.1mg / kg, i.p.) at ...

Embodiment 3

[0171] Example 3, CysLT 2 Protective effect of intraperitoneal injection of R selective antagonist HAMI 3379 on chronic injury of focal cerebral ischemia in rats

[0172] 1. Behavioral changes

[0173] Within 14 days after MCAO, neurological symptoms and sensory-motor deficits were evaluated on the 1st, 3rd, 5th, 7th, 10th, and 14th day. The rats in the sham operation group had no neurological symptoms within 14 days after operation. In rats with cerebral ischemia in the normal saline group, the neurological symptom score was the highest at 24 hours after MCAO, gradually decreased within 7 days, and basically reached the lowest level after 10 days and maintained until 14 days. The neurological symptom score of rats within 7 days after MCAO ( Figure 15 A). In the slant plate test, the angle of the slant plate in the sham operation group was relatively stable 14 days after operation, and the change trend of the angle of the slant plate in the normal saline group was c...

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Abstract

The invention provides applications of a receptor antagonist in treating focal cerebral ischemia injuries, and belongs to the technical field of biological medicine. In rat focal cerebral ischemia models, HAMI 3379 intracerebroventricular administration possesses protection effects on acute injuries of the rat focal cerebral ischemia models; HAMI 3379 intraperitoneal injection administration possesses protection effects on accurate and subacute injuries, and at the same time, inflammatory reaction is reduced, and especially microglial cell activation is inhibited; and HAMI 3379 intraperitoneal injection administration possesses protection effects on cerebral ischemia chronic injuries, and neurological function recovery can be promoted.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to the application of a receptor antagonist in the treatment of focal cerebral ischemic injury, specifically including the administration of HAMI 3379 in the lateral ventricle of the focal cerebral ischemic injury in rats. Acute injury in the cerebral ischemia model has a protective effect; intraperitoneal injection of HAMI 3379 also has a protective effect on acute and subacute injury, and can reduce inflammation, especially inhibit the activation of microglial cells; intraperitoneal injection of HAMI 3379 has a protective effect on Chronic cerebral ischemic injury still has a protective effect and can promote the recovery of neurological function. Background technique [0002] Inflammatory changes after cerebral ischemia-reperfusion are one of the important foundations of brain injury. Cerebral ischemia-reperfusion injury is a highly complex pathological process, and ischemia i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/196A61P9/10A61P29/00A61P25/00A61P7/10
Inventor 石巧娟李巍卢领群楼琦郭红刚黄河儒刘月环应华忠魏尔清
Owner ZHEJIANG ACAD OF MEDICAL SCI
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