Impaired spatial learning in a novel rat model of mild cerebral concussion injury

Abstract

The aim of the present study was to develop a model of mild traumatic brain injury in the rat that mimics human concussive brain injury suitable to study pathophysiology and potential treatments. 34 male Wistar rats received a closed head trauma (TBI) and 30 animals served as controls (CON). Immediately following trauma, animals lost their muscle tone and righting reflex response, recovering from the latter within 11.4 +/- 8.2 min. Corneal reflex and whisker responses returned within 4.5 +/- 3.0 min and 6.1 +/- 2.9 min, respectively. The impact resulted in a short transient decrease of pO2 (P < 0.001), increase in mean arterial blood pressure (P = 0.026), and a reduction of heart rate (P < 0.01). Serial MRI did not show any abnormalities across the entire cerebrum on diffusion, T1, T2, and T2*-weighted images at all investigated time points. TBI animals needed significantly longer to locate the hidden platform in a Morris water maze and spent less time in the training quadrant than controls. TBI led to a significant neuronal loss in frontal cortex (P < 0.001), as well as hippocampal CA3 (P = 0.017) and CA1 (P = 0.002) at 9 days after the trauma; however, cytoskeletal architecture was preserved as indicated by normal betaAPP- and MAP-2 staining. We present a unique, noninvasive rat model of mild closed head trauma with characteristics of human concussion injury, including brief loss of consciousness, cognitive impairment, and minor brain injury.