Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Compositions and methods for treating traumatic brain injury

A traumatic, post-brain injury technique for use in the field of agents to reduce necrotizing neuronal cell death, addressing issues such as short treatment time windows

Active Publication Date: 2016-12-21
陈锦辉
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In large part, the failure of these treatments may be due to the very short treatment time window after traumatic brain injury, or the difficulty of the compounds used to cross the blood-brain barrier (BBB) ​​into the brain

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Compositions and methods for treating traumatic brain injury
  • Compositions and methods for treating traumatic brain injury
  • Compositions and methods for treating traumatic brain injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0095] Example 1 - Death-associated kinase (DAPK) 1 phosphorylates NMDA receptor 2B subtype (NR2B) at S1303 in neurons after traumatic brain injury

[0096] Adult mice received a moderate level of impact on the left side of the brain, producing moderately traumatic CCI TBI. The location and parameters of impact are shown in the schematic diagram ( figure 1 described in a). In the sham-operated control mice, no loss of brain tissue was seen. 24 hours after a moderate level of CCI injury, the ipsilateral cortex exhibited typical tissue loss ( figure 1 b). In sham-operated control mice, immunostaining ( figure 1 In c, C1-C2), the levels of phosphorylated NR2B S1303 (pNR2B) and DAPK kinase are barely detectable. However, at 24 hours after injury, the levels of pNR2B and kinases were significantly upregulated in cells adjacent to the injury ( figure 1 c, C3-4). DAPI staining showed their nuclear condensation. The activated kinase is present in the cytoplasm, while pNR2B is ...

Embodiment 2

[0098] Example 2 - Treatment of neurons with TNR0118 reduces glutamate-induced Ca2+ influx and protects glutamate-induced neuronal hyperexcitatory death in vitro

[0099] It has been demonstrated that DAPK1 kinase can bind to the C-terminus of NR2B and phosphorylate NR2B at Ser-1303, thereby enhancing the response of NMDA receptors to Ca 2+ the permeability. Excess Ca 2+ Influx further activates DAPK1, which in turn enhances the response of NMDA receptors to Ca by phosphorylating NR2B 2+ The permeability of the nerves forms a harmful vicious circle, which leads to the excessive excitatory death of the nerves. In a variety of neurological diseases, including traumatic brain injury, neuronal cell death is due to glutamate receptor-associated excess Ca 2+ Caused by inflow [35, 36, 67].

[0100] To test whether the inhibition of glutamate-induced phosphorylation of NR2B by TNR0118 could prevent Ca 2+ Influx, reduce excess intracellular Ca 2+ To investigate the cytotoxicity i...

Embodiment 3

[0103] Example 3 - A single intravenous injection of TNR10118 after TBI reduces TBI-induced cerebral cortex damage

[0104] All animals received moderate traumatic brain injury (TBI) and were then randomly assigned to PBS control, scrambled control peptide and treatment groups [22, 48, 56, 68]. One hour after wounding, mice received intravenous injections of PBS, control peptide (10 mg / kg body weight), or TNR10118 (10 mg / kg body weight), respectively. Twenty-four hours after injection, mice were sacrificed and the size of their cerebral cortical lesion volumes were determined using the Cavalieri method.

[0105] Each animal suffered a moderate traumatic brain injury, and all showed obvious cerebral cortex defects at the traumatized site ( Figure 4 a-c). We first measured the volume of cortical lesions to assess the therapeutic effect of short peptides. Control animals that received PBS injection showed obvious cortical tissue defects ( Figure 4 a). Compared with the cor...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a method for inhibiting damage to a neural cell following traumatic brain injury. The method comprises the step of exposing at least one neural cell to an effective amount of pharmaceutical agent that inhibits N-methyl D-Aspartate receptor 2B subtype (NR2B) activity by uncoupling its binding with DAPKl, whereby the damage to the at least one neural cell is inhibited.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Provisional Application No. 61 / 558,171, entitled "Compositions and Methods for Treating Neural Injuries," filed November 10, 2011, the entire contents of which are incorporated herein by reference. technical field [0003] The present application relates generally to methods for attenuating cortical damage and promoting functional recovery following traumatic brain injury, particularly methods utilizing agents capable of reducing necrotic neuronal cell death by inhibiting NMDA receptor phosphorylation. Background technique [0004] Mild to severe traumatic brain injury (TBI) events occur annually in the United States [1,2]. That number is six times the number of cases of multiple sclerosis, spinal cord injury, AIDS and breast cancer combined. In addition, it is estimated that more than 300,000 US veterans of the Iraq and Afghanistan wars suffered from long-term TBI due to expo...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/10A61P25/00
CPCA61K38/10A61P25/00A61P25/28
Inventor 陈锦辉
Owner 陈锦辉
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com