The pathobiology of moderate diffuse traumatic brain injury as identified using a new experimental model of injury in...

Experimental models of traumatic brain injury have been developed to replicate selected aspects of human head injury, such as contusion, concussion, and/or diffuse axonal injury. Although diffuse axonal injury is a major feature of clinical head injury, relatively few experimental models of diffuse traumatic brain injury (TBI) have been developed, particularly in smaller animals such as rodents. Here, we describe the pathophysiological consequences of moderate diffuse TBI in rats generated by a newly developed, highly controlled, and reproducible model. This model of TBI caused brain edema beginning 20 min after injury and peaking at 24 h post-trauma, as shown by wet weight/dry weight ratios and diffusion-weighted magnetic resonance imaging. Increased permeability of the blood-brain barrier was present up to 4 h post-injury as evaluated using Evans blue dye. Phosphorus magnetic resonance spectroscopy showed significant declines in brain-free magnesium concentration and reduced cytosolic phosphorylation potential at 4 h post-injury. Diffuse axonal damage was demonstrated using manganese-enhanced magnetic resonance imaging, and intracerebral injection of a fluorescent vital dye (Fluoro-Ruby) at 24-h and 7-day post-injury. Morphological evidence of apoptosis and caspase-3 activation were also found in the cerebral hemisphere and brainstem at 24 h after trauma. These results show that this model is capable of reproducing major biochemical and neurological changes of diffuse clinical TBI.