Considerations for Experimental Animal Models of Concussion, Traumatic Brain
Injury, and Chronic Traumatic Encephalopathy-These Matters Matter
#MMPMID28620350
Wojnarowicz MW
; Fisher AM
; Minaeva O
; Goldstein LE
Front Neurol
2017[]; 8
(?): 240
PMID28620350
show ga
Animal models of concussion, traumatic brain injury (TBI), and chronic traumatic
encephalopathy (CTE) are widely available and routinely deployed in laboratories
around the world. Effective animal modeling requires careful consideration of
four basic principles. First, animal model use must be guided by clarity of
definitions regarding the human disease or condition being modeled. Concussion,
TBI, and CTE represent distinct clinical entities that require clear
differentiation: concussion is a neurological syndrome, TBI is a neurological
event, and CTE is a neurological disease. While these conditions are all
associated with head injury, the pathophysiology, clinical course, and medical
management of each are distinct. Investigators who use animal models of these
conditions must take into account these clinical distinctions to avoid
misinterpretation of results and category mistakes. Second, model selection must
be grounded by clarity of purpose with respect to experimental questions and
frame of reference of the investigation. Distinguishing injury context ("inputs")
from injury consequences ("outputs") may be helpful during animal model
selection, experimental design and execution, and interpretation of results.
Vigilance is required to rout out, or rigorously control for, model artifacts
with potential to interfere with primary endpoints. The widespread use of
anesthetics in many animal models illustrates the many ways that model artifacts
can confound preclinical results. Third, concordance between key features of the
animal model and the human disease or condition being modeled is required to
confirm model biofidelity. Fourth, experimental results observed in animals must
be confirmed in human subjects for model validation. Adherence to these
principles serves as a bulwark against flawed interpretation of results, study
replication failure, and confusion in the field. Implementing these principles
will advance basic science discovery and accelerate clinical translation to
benefit people affected by concussion, TBI, and CTE.
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