Transcranial amelioration of inflammation and cell death after brain injury.
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| Title: | Transcranial amelioration of inflammation and cell death after brain injury. |
|---|---|
| Authors: | Roth, Theodore L., Nayak, Debasis, Atanasijevic, Tatjana, Koretsky, Alan P., Latour, Lawrence L., McGavern, Dorian B. |
| Source: | Nature. 1/9/2014, Vol. 505 Issue 7482, p223-228. 6p. 3 Color Photographs, 2 Graphs. |
| Subjects: | Brain injuries, Inflammation, Cell death, Neurophysiology, Reactive oxygen species, Small molecules |
| Abstract: | Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function. At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury. [ABSTRACT FROM AUTHOR] |
| Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 93598322 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=93598322 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/nature12808 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 6 StartPage: 223 Subjects: – SubjectFull: Brain injuries Type: general – SubjectFull: Inflammation Type: general – SubjectFull: Cell death Type: general – SubjectFull: Neurophysiology Type: general – SubjectFull: Reactive oxygen species Type: general – SubjectFull: Small molecules Type: general Titles: – TitleFull: Transcranial amelioration of inflammation and cell death after brain injury. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Roth, Theodore L. – PersonEntity: Name: NameFull: Nayak, Debasis – PersonEntity: Name: NameFull: Atanasijevic, Tatjana – PersonEntity: Name: NameFull: Koretsky, Alan P. – PersonEntity: Name: NameFull: Latour, Lawrence L. – PersonEntity: Name: NameFull: McGavern, Dorian B. IsPartOfRelationships: – BibEntity: Dates: – D: 09 M: 01 Text: 1/9/2014 Type: published Y: 2014 Identifiers: – Type: issn-print Value: 00280836 Numbering: – Type: volume Value: 505 – Type: issue Value: 7482 Titles: – TitleFull: Nature Type: main |
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