Open AccessDiverse changes in microglia morphology and axonal pathology during the course of 1 year after mild traumatic brain injury in pigs
Author(s) -
Grovola Michael R.,
Paleologos Nicholas,
Brown Daniel P.,
Tran Nathan,
Wofford Kathryn L.,
Harris James P.,
Browne Kevin D.,
Shewokis Patricia A.,
Wolf John A.,
Cullen D. Kacy,
Duda John E.
Publication year - 2021
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12953
Subject(s) - traumatic brain injury , pathology , astrocyte , microglia , white matter , corpus callosum , diffuse axonal injury , chronic traumatic encephalopathy , medicine , neuroscience , neuroinflammation , biology , central nervous system , poison control , disease , magnetic resonance imaging , inflammation , concussion , injury prevention , environmental health , radiology , psychiatry
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 are caused by 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 the 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 the 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.