http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12808.html
- Nature
- doi:10.1038/nature12808
- Received
- Accepted
- Published online
Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function1, 2.
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.
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