Object: The authors describe an experimental model of closed head injury in rodents that was modified from one developed by Marmarou and colleagues. This modification allows dual control of the dynamic process of impact compared with impulse loading that occurs at the moment of primary brain injury. The principal element in this weight-drop model is an adjustable table that supports the rat at the moment of impact from weights positioned at different heights (accelerations). The aim was to obtain reproducible pathological intracranial pressure (ICPs) while maximally reducing the incidence of mortality and skull fractures.
Methods: Intracranial pressure was investigated in different experimental settings, including two different rat strains and various impact-acceleration conditions and posttrauma survival times. Identical impact-acceleration injuries produced a considerably higher mortality rate in Wistar rats than in Sprague-Dawley rats (50% and 0%, respectively). Gradually increasing severity of impact-acceleration conditions resulted in findings of a significant correlation between the degree of traumatic challenge and increased ICP at 4 hours (p < 0.001, R2=0.73). When the impact-acceleration ratio was changed to result in a more severe head injury, the ICP at 4, 24, and 72 hours was significantly elevated in comparison with that seen in sham-injured rats (4 hours: 19.7+/-2.8 mm Hg, p=0.004; 24 hours: 21.8+/-1.1 mm Hg, p=0.002; 72 hours: 11.9+/-2.5 mm Hg, p=0.009). Comparison of the rise in ICP between moderate and severe impact-acceleration injury at 4 and 24 hours revealed a significantly higher value after severe injury (4 hours: p=0.008; 24 hours: p=0.004). Continuous recordings showed that ICP mounted very rapidly to peak values, which declined gradually toward a pathological level dependent on the severity of the primary insult. Histological examination after severe trauma revealed evidence of irreversible neuronal necrosis, diffuse axonal injury, petechial bleeding, glial swelling, and perivascular edema.
Conclusions: This modified closed head injury model mimics several clinical features of traumatic injury and produces reliable, predictable, and reproducible ICP elevations with concomitant morphological alterations.