Impaired spatial learning in a novel rat model of mild cerebral concussion injury.
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.
Henninger
Nils
N
Department of Neurology, University of Heidelberg, 69120 Heidelberg, Germany. nils.henninger@umassmed.edu
Dützmann
Stephan
S
Sicard
Kenneth M
KM
Kollmar
Rainer
R
Bardutzky
Jürgen
J
Schwab
Stefan
S
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001924:Brain Concussion / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D002452:Cell Count / Q000379:methods; D016923:Cell Death; D004195:Disease Models, Animal; D006339:Heart Rate / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D007859:Learning Disabilities / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior / Q000502:physiology*; D013997:Time Factors
C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins