A Novel Quantitative Mice Model of Penetrating Traumatic Brain Injury

Background: Traumatic brain injury (TBI) is a major cause of mortality and
disability in humans. . In animal models of TBI, injury is produced by a severe
mechanical impact to the head, conditions in which the dimensions and severity of the
damage to the brain are uncontrolled and produce experimental inconsistencies. We
developed a new model in mice, which provides such a control and improves
quantitation of TBI.
Results: In the new model, the location, dimensions and severity of the damage are
precise and replicable. The site - chosen using a stereotactic apparatus, dimensions -
determined by drilling into the soft tissue to specific depths using drills of defined
calibers. We tested cortical wounds (1.8-2.3 caliber, 1.5-2.5mm depth) and found
them all to bear TBI characteristics (e.g. inflammation, scar, cell death). This injury
procedure enabled selection of particular impairment of interest, with minimal
contamination of non-desired malfunctions. For example, injury within the motor
cortex (1mm anterior, 1mm right to bregma, 2.3 mm diameter, 2 mm depth) resulted
in motor impairment (4 in neurological severity score) with negligible effect on
anxiety (open field) compared to untreated animals. Vice versa, a same size wound in
the cerebral cortex (2mm posterior, 2mm right to bregma) elevated anxiety 1.5 fold
above the level of control animals, with a no effect on motor function.
Conclusions: Such high consistency and control over the location and spread of
damage during TBI increases the capacity to study this type of injury and develop
proper treatments.