Pham, Louise, Shultz, Sandy R., Kim, Hyun Ah, Brady, Rhys D., Wortman, Ryan C., Genders, Shannyn G., Hale, Matthew W., O'Shea, Ross D., Djouma, Elvan, van den Buuse, Maarten, Church, Jarrod E., Christie, Brian R., Drummond, Grant R., Sobey, Christopher G., and McDonald, Stuart J. (2019) Mild closed-head injury in conscious rats causes transient neurobehavioral and glial disturbances: a novel experimental model of concussion. Journal of Neurotrauma, 36 (14). pp. 2260-2271.

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Abstract

Rodent models can provide insights into the most pertinent issues surrounding concussion. Nonetheless, the relevance of some existing models to clinical concussion can be questioned, particularly with regard to the use of surgery and anesthesia and the mechanism and severity of injury. Accordingly, we have co-developed an awake closed-head injury (ACHI) model in rats. Here, we aimed to create a temporal profile of the neurobehavioral and neuropathological effects of a single ACHI. Adolescent male rats were placed in a restraint bag and a steel helmet was positioned over the head such that the impact target was centered over the left parietal cortex. Once positioned on a foam platform, a cortical impactor was used to strike the helmet. Sham animals underwent the same procedure without impact. When compared with sham rats, those given a single ACHI displayed evidence of sensorimotor deficits and reduced exploratory behavior within the first 20 min post-injury; however, these effects were resolved after 24 h. A single ACHI impaired spatial memory on the Y-maze task at both 5 min and 24 h post-ACHI; however, no deficits were apparent at 48 h. Immunostaining revealed region-specific increases in ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein expression at 3 days post-impact, with no differences found at either 1 or 14 days. Taken together, our findings indicate that a single ACHI results in transient neurobehavioral and glial disturbances and as such, this model may be a valuable tool for pre-clinical concussion research.

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