Development and evaluation of a diffuse axonal injury modeling device in rats

Objectives To develop a rat diffuse axonal injury (DAI) modeling device and to evaluate its molding effect. Methods A total of 20 adult male SD rats were randomly divided into either a control group (n=5) or a DAI model group (n=15). A rat DAI model was prepared by using a coronal rotation device. The neurological severity scores (NSS) were performed using 6 h, 24 h, and 7 d time points after modeling. HE staining and silver staining were used to observe the morphology changes of brain tissue. Immunohistochemical staining was used to detect the expression of β-amyloid precursor protein (β-APP) in brain tissue after DAI. Results Rats showed varying degrees of coma after DAI. They showed no autonomic activities, stinging reflex, and dullness of pupillary light reflex. The coma lasted for about 50 min to 4 h. After awakening, all rats showed reduced activities, unresponsiveness, not eating, and unstable walking. NSS at each time point (6 h, 9.33±0.88, 24 h, 5.67±0.67, and 7 d, 4.67±0.88) was higher than that of the control group (6 h, 1.33±0.67, 24 h, 0±0, and 7d, 0±0) (P<0.05). HE staining showed that the number of cells in the cortex (6 h, 323.33±95.82, 24 h, 294.00±54.98, and 7 d, 277.83±52.26), hippocampus (7 d, 214.50±43.69) and brainstem (6 h, 326.67±102.80; 24 h, 298.33±67.56; 7d, 234.50±18.20) of the DAI model group were significantly reduced compared with that in the cortex (430.33±20.35), hippocampus (327.17±24.34), and brainstem (429.50±81.86) of the control groups (the cell number of brainstem of the DAI 6 h model group [P<0.05], the cell number other DAI model subgroups [P<0.01]), karyopyknosis, and glial cell proliferation were found. In the cortex and around brainstem neurons, a large number of vacuolations and a few bleeding points were observed. The traveling disorders of brainstem nerve fibers were also observed. Silver staining displayed the brainstem axonal string-of-beads axonal ball formation. Immunohistochemical staining showed that the β-APP expression in the cortex (24 h, 9.16±1.32; 7 d, 14.50±2.83), hippocampus (24 h, 10.14±2.56; 7 d, 12.50±1.95), and brainstem (6 h, 6.74±1.33; 24 h, 7.64±1.11; 10.09±1.77) of the DAI model group were significantly higher than those in the cortex (4.02±0.34), hippocampus (4.26±0.70), and brainstem (4.38±0.85) of the control groups (P<0.01), and they increased with the prolonged time of injury after DAI. Conclusions This device is able to cause rat brain DAI, and it has the characteristics of simple, controllable, and precise. It can be used in the experimental studies of DAI model in rats. Key words: Diffuse axonal injury; Modeling device; Rats; Development; Evaluation