RT Journal Article
SR Electronic
T1 Diverse Changes in Microglia Morphology and Axonal Pathology Over One Year after Mild Traumatic Brain Injury in Pigs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.16.343103
DO 10.1101/2020.10.16.343103
A1 Michael R. Grovola
A1 Nicholas Paleologos
A1 Daniel P. Brown
A1 Nathan Tran
A1 Kathryn L. Wofford
A1 James P. Harris
A1 Kevin D. Browne
A1 John A. Wolf
A1 D. Kacy Cullen
A1 John E. Duda
YR 2020
UL http://biorxiv.org/content/early/2020/10/17/2020.10.16.343103.abstract
AB Over 2.8 million people experience mild traumatic brain injury (TBI) in the United States each year, which may lead to long-term neurological dysfunction. The mechanical forces that occur due to TBI propagate through the brain to produce diffuse axonal injury (DAI) and trigger secondary neuroinflammatory cascades. The cascades may persist from acute to chronic time points after injury, altering the homeostasis of the brain. However, the relationship between the hallmark axonal pathology of diffuse TBI and potential changes in glial cell activation or morphology have not been established in a clinically relevant large animal model at chronic time points. In this study, we assessed tissue from pigs subjected to rapid head rotation in the coronal plane to generate mild TBI. Neuropathological assessments for axonal pathology, microglial morphological changes, and astrocyte reactivity were conducted in specimens out to 1 year post injury. We detected an increase in overall amyloid precursor protein pathology, as well as periventricular white matter and fimbria/fornix pathology after a single mild TBI. We did not detect changes in corpus callosum integrity or astrocyte reactivity. However, detailed microglial skeletal analysis revealed changes in morphology, most notably increases in the number of microglial branches, junctions, and endpoints. These subtle changes were most evident in periventricular white matter and certain hippocampal subfields, and were observed out to 1 year post injury in some cases. These ongoing morphological alterations suggest persistent change in neuroimmune homeostasis. Additional studies are needed to characterize the underlying molecular and neurophysiological alterations, as well as potential contributions to neurological deficits.Competing Interest StatementThe authors have declared no competing interest.