Ahead of Print: Elucidating the Severity of Preclinical TBI Models

Background: Concussion remains a symptom-based diagnosis clinically, yet preclinical studies investigating traumatic brain injury, of which concussion is believed to represent a ‘mild’ form, emphasize histological endpoints with functional assessments often minimized or ignored all together. Recently, clinical studies have identified the importance of cognitive and neuropsychiatric symptoms, in addition to somatic complaints, following concussion. How these findings may translate to preclinical studies is unclear at present.

Objective: To address the contrasting endpoints utilized clinically compared to those in preclinical studies and the potential role of functional assessments in a commonly used model of diffuse axonal injury (DAI).

Methods: Animals were subjected to DAI using the impact-acceleration model. Functional and behavioral assessments were conducted over 1 week following DAI prior to completion of histological assessment at 1-week post-DAI.

Results: We show, despite the suggestion that this model represents concussive injury, no functional impairments as determined using common measures of motor, sensorimotor, cognitive, and neuropsychiatric function following injury over the course of 1 week. The lack of functional deficits is in sharp contrast to neuropathologic findings indicating neural degeneration, astrocyte reactivity, and microglial activation.

Conclusion: Future studies are needed to identify functional assessments, neurophysiologic techniques, and imaging assessments more apt to distinguish differences following so-called ‘mild’ traumatic brain injury (TBI) in preclinical models and determine whether these models are truly studying concussive or subconcussive injury. These studies are needed to not only understand mechanism of injury and production of subsequent deficits, but also for rigorous evaluation of potential therapeutic agents.

From: Elucidating the Severity of Preclinical Traumatic Brain Injury Models: A Role for Functional Assessment? by Rosen et al.

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