TY - JOUR
T1 - Expression of GFAP and Tau Following Blast Exposure in the Cerebral Cortex of Ferrets
AU - Schwerin, Susan C.
AU - Chatterjee, Mitali
AU - Hutchinson, Elizabeth B.
AU - Djankpa, Francis T.
AU - Armstrong, Regina C.
AU - McCabe, Joseph T.
AU - Perl, Daniel P.
AU - Juliano, Sharon L.
N1 - Funding Information:
This study was supported by the Center for Neuroscience and Regenerative Medicine-CNRM-70-8956, USU-PAT-74-3439, and the Congressionally Directed Medical Research Program W81XWH-13-2-0018. The authors thank CNRM for core facility support enabling this work, specifically the Advanced Blast Simulator (with Yeonho Kim and Amanda Fu) and the translational imaging facility. They also thank Dr. Aviva Symes for helpful comments on the manuscript.
Publisher Copyright:
© 2021 American Association of Neuropathologists, Inc.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - Blast exposures are a hallmark of contemporary military conflicts. We need improved preclinical models of blast traumatic brain injury for translation of pharmaceutical and therapeutic protocols. Compared with rodents, the ferret brain is larger, has substantial sulci, gyri, a higher white to gray matter ratio, and the hippocampus in a ventral position; these attributes facilitate comparison with the human brain. In this study, ferrets received compressed air shock waves and subsequent evaluation of glia and forms of tau following survival of up to 12 weeks. Immunohistochemistry and Western blot demonstrated altered distributions of astrogliosis and tau expression after blast exposure. Many aspects of the astrogliosis corresponded to human pathology: increased subpial reactivity, gliosis at gray-white matter interfaces, and extensive outlining of blood vessels. MRI analysis showed numerous hypointensities occurring in the 12-week survival animals, appearing to correspond to luminal expansions of blood vessels. Changes in forms of tau, including phosphorylated tau, and the isoforms 3R and 4R were noted using immunohistochemistry and Western blot in specific regions of the cerebral cortex. Of particular interest were the 3R and 4R isoforms, which modified their ratio after blast. Our data strongly support the ferret as an animal model with highly translational features to study blast injury.
AB - Blast exposures are a hallmark of contemporary military conflicts. We need improved preclinical models of blast traumatic brain injury for translation of pharmaceutical and therapeutic protocols. Compared with rodents, the ferret brain is larger, has substantial sulci, gyri, a higher white to gray matter ratio, and the hippocampus in a ventral position; these attributes facilitate comparison with the human brain. In this study, ferrets received compressed air shock waves and subsequent evaluation of glia and forms of tau following survival of up to 12 weeks. Immunohistochemistry and Western blot demonstrated altered distributions of astrogliosis and tau expression after blast exposure. Many aspects of the astrogliosis corresponded to human pathology: increased subpial reactivity, gliosis at gray-white matter interfaces, and extensive outlining of blood vessels. MRI analysis showed numerous hypointensities occurring in the 12-week survival animals, appearing to correspond to luminal expansions of blood vessels. Changes in forms of tau, including phosphorylated tau, and the isoforms 3R and 4R were noted using immunohistochemistry and Western blot in specific regions of the cerebral cortex. Of particular interest were the 3R and 4R isoforms, which modified their ratio after blast. Our data strongly support the ferret as an animal model with highly translational features to study blast injury.
KW - Aquaporin
KW - Astrocyte
KW - Blood vessels
KW - Phosphorylated tau
KW - Pia
KW - Tau isoforms
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U2 - 10.1093/jnen/nlaa157
DO - 10.1093/jnen/nlaa157
M3 - Article
C2 - 33421075
AN - SCOPUS:85100358222
SN - 0022-3069
VL - 80
SP - 112
EP - 128
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 2
ER -