Juvenile mild traumatic brain injury elicits distinct spatiotemporal astrocyte responses
Glia. 2019-10-31; :
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Clément T(1), Lee JB(2), Ichkova A(1), Rodriguez-Grande B(1), Fournier ML(1), Aussudre J(1), Ogier M(3), Haddad E(4), Canini F(3), Koehl M(5), Abrous DN(5), Obenaus A(2)(4), Badaut J(1)(2).
(1)CNRS UMR5287, University of Bordeaux, Bordeaux, France.
(2)Department of Physiology, Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.
(3)Département des Neurosciences et Sciences Cognitives, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France.
(4)Department of Pediatrics, University of California, Irvine, Irvine, California.
(5)Neurocentre Magendie INSERM U1215, Bordeaux, France.
Mild-traumatic brain injury (mTBI) represents ~80% of all emergency room visits
and increases the probability of developing long-term cognitive disorders in
children. To date, molecular and cellular mechanisms underlying post-mTBI
cognitive dysfunction are unknown. Astrogliosis has been shown to significantly
alter astrocytes’ properties following brain injury, potentially leading to
significant brain dysfunction. However, such alterations have never been
investigated in the context of juvenile mTBI (jmTBI). A closed-head injury model
was used to study jmTBI on postnatal-day 17 mice. Astrogliosis was evaluated
using glial fibrillary acidic protein (GFAP), vimentin, and nestin immunolabeling
in somatosensory cortex (SSC), dentate gyrus (DG), amygdala (AMY), and
infralimbic area (ILA) of prefrontal cortex in both hemispheres from 1 to 30 days
postinjury (dpi). In vivo T2-weighted-imaging (T2WI) and diffusion tensor imaging
(DTI) were performed at 7 and 30 dpi to examine tissue level structural
alterations. Increased GFAP-labeling was observed up to 30 dpi in the ipsilateral
SSC, the initial site of the impact. However, vimentin and nestin expression was
not perturbed by jmTBI. The morphology of GFAP positive cells was significantly
altered in the SSC, DG, AMY, and ILA up to 7 dpi that some correlated with
magnetic resonance imaging changes. T2WI and DTI values were significantly
altered at 30 dpi within these brain regions most prominently in regions distant
from the impact site. Our data show that jmTBI triggers changes in astrocytic
phenotype with a distinct spatiotemporal pattern. We speculate that the presence
and time course of astrogliosis may contribute to pathophysiological processes
and long-term structural alterations following jmTBI.
© 2019 Wiley Periodicals, Inc.