Transcranial amelioration of inflammation and cell death after brain injury View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-01

AUTHORS

Theodore L. Roth, Debasis Nayak, Tatjana Atanasijevic, Alan P. Koretsky, Lawrence L. Latour, Dorian B. McGavern

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. More... »

PAGES

223

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature12808

DOI

http://dx.doi.org/10.1038/nature12808

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050073740

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24317693


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