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Compositions and methods of treating and preventing neuronal damage from traumatic brain injury

A brain-injured and traumatic technology, applied in drug combinations, neurological diseases, pharmaceutical formulations, etc., can solve problems that have not yet been effectively treated

Active Publication Date: 2015-09-09
陈锦辉
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are currently no FDA-approved effective treatments for post-TBI symptoms

Method used

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  • Compositions and methods of treating and preventing neuronal damage from traumatic brain injury
  • Compositions and methods of treating and preventing neuronal damage from traumatic brain injury
  • Compositions and methods of treating and preventing neuronal damage from traumatic brain injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Example 1: DHF can protect neurons from cell excitotoxicity in vitro.

[0051] This example is to examine the neuroprotective effect of DHF in excitotoxic injury of cells, and the optimal dose in cells in vitro.

[0052] Hippocampal cell culture and in vitro TBI modeling. Brains of C57BL / 6 mice (postnatal day (P0)) were dissected, meninges were removed, and hippocampus was isolated. Hippocampal tissue was digested with papain, and single cells were harvested, plated on coverslips pretreated with lysine, and treated with B27Neurobasal TM Cultured in serum-free medium (Brewer et al., 1993). In order to simulate trauma in vivo, cells isolated for 5 days (DIV5) were treated with 100 μM glutamate and 20 μM glycine, and a group of cells were treated with the same volume of DMSO as a control for 60 minutes and then left for 24 hours.

[0053] DHF treatment. Thirty minutes before glutamic acid and glycine treatment, the cells were treated with DHF (dissolved in DMSO, the fi...

Embodiment 2

[0060] Example 2: DHF reduces cortical deficits after TBI

[0061] DHF is a small molecule (molecular weight of 254.25 g / mol) that can cross the blood-brain barrier to reach brain regions, thereby affecting the damage of TBI (Andero et al., 2011). Here DHF was administered by intraperitoneal injection to test whether DHF administration can reduce the death of cortical neurons after TBI in an in vivo model.

[0062] method

[0063] animal. Male C57BL / 6 mice (The Jackson Laboratories, Bar Harbor, ME) were given a 12 / 12-hour light / dark cycle environment and had adequate access to food and water. Mice aged 8-10 weeks were selected for modeling. All procedures were performed in accordance with the protocols of the Animal Care and Use Committee of Indiana University.

[0064] TBI modeling. C57BL / 6 mice aged 8-10 weeks were used to model TBI. The mouse was fixed on a stereotaxic instrument, the scalp was cut, and the intersection point of the line connecting the anterior and po...

Embodiment 3

[0072]Example 3: DHF reduces the death of immature neurons after TBI and increases the newly born immature neurons in the hippocampus

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Abstract

Methods and compounds for treating, inhibiting, and preventing traumatic brain injury are provided. Methods include administering 7,8-dihydroxyflavone and derivatives thereof.

Description

[0001] government interest [0002] This invention was supported by the US National Institutes of Health, Grant No. NS072631. The government has certain rights in this invention. Background technique [0003] Traumatic brain injury (TBI) is a leading cause of death and disability in children and young adults (Aitken et al., 2009; McCarthy et al., 2006). TBI induces neuronal death in the brain, including hippocampal and cortical regions. TBI can not only cause primary injury through direct tissue loss (Hall et al., 2004; Hall et al., 2005b; Singh et al., 2006), but also secondary injury in surviving cells through this primary event (Faden et al., 1989 ; Fujimoto et al., 2004b; Hall et al., 2005b; Marion et al., 1997). Lesions widely exist in brain tissue, such as the cerebral cortex and hippocampus, and this injury has been observed in humans (Ariza et al., 2006; Bigler et al., 1997; Isoniemi et al., 2006; Tate and Bigler, 2000; Umile et al., 2002; Wilde et al., 2007 ) and ...

Claims

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Application Information

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IPC IPC(8): A61K31/353A61P25/24
CPCA61K31/352A23L2/52A61P25/24
Inventor 陈锦辉
Owner 陈锦辉
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