Mossy cell hypertrophy and synaptic changes in the hilus following mild diffuse traumatic brain injury in pigs

Autor: Michael R. Grovola, Nicholas Paleologos, Kathryn L. Wofford, James P. Harris, Kevin D. Browne, Victoria Johnson, John E. Duda, John A. Wolf, D. Kacy Cullen
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-18 (2020)
Druh dokumentu: article
ISSN: 1742-2094
DOI: 10.1186/s12974-020-1720-0
Popis: Abstract Background Each year in the USA, over 2.4 million people experience mild traumatic brain injury (TBI), which can induce long-term neurological deficits. The dentate gyrus of the hippocampus is notably susceptible to damage following TBI, as hilar mossy cell changes in particular may contribute to post-TBI dysfunction. Moreover, microglial activation after TBI may play a role in hippocampal circuit and/or synaptic remodeling; however, the potential effects of chronic microglial changes are currently unknown. The objective of the current study was to assess neuropathological and neuroinflammatory changes in subregions of the dentate gyrus at acute to chronic time points following mild TBI using an established model of closed-head rotational acceleration induced TBI in pigs. Methods This study utilized archival tissue of pigs which were subjected to sham conditions or rapid head rotation in the coronal plane to generate mild TBI. A quantitative assessment of neuropathological changes in the hippocampus was performed via immunohistochemical labeling of whole coronal tissue sections at 3 days post-injury (DPI), 7 DPI, 30 DPI, and 1 year post-injury (YPI), with a focus on mossy cell atrophy and synaptic reorganization, in context with microglial alterations (e.g., density, proximity to mossy cells) in the dentate gyrus. Results There were no changes in mossy cell density between sham and injured animals, indicating no frank loss of mossy cells at the mild injury level evaluated. However, we found significant mossy cell hypertrophy at 7 DPI and 30 DPI in anterior (> 16% increase in mean cell area at each time; p =
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