Neutrophil Accumulation After Traumatic Brain Injury in Rats: Comparison of Weight Drop and Controlled Cortical Impact Models

Abstract

Previous work in our laboratory and others using the weight drop (WD) model of traumatic brain injury (TBI) has shown that neutrophils accumulate in brain tissue during the initial 24 h posttrauma as measured by myeloperoxidase (MPO) activity and immunohistochemistry. This study compares the acute inflammatory response to TBI over time, as measured by MPO activity, in the WD and controlled cortical impact (CCI) models. Anesthetized adult Sprague-Dawley rats were traumatized using WD (10-g weight dropped 5 cm) or CCI (4 m/sec, 2.5 mm depth). At 2, 24, 48, or 168 h after trauma, rats (n = 4–5/group at each time) were anesthetized and killed, the brains were removed, and 6-mm coronal slices from traumatized and contralateral hemispheres were assayed for MPO activity. Nontraumatized rats (n = 4) served as controls. Three additional rats underwent a more severe CCI (3 mm depth) with MPO activity assayed at 24 h. A separate group of rats (n = 6) was subjected to WD trauma and killed at 2 weeks after injury for analysis of lesion volume. MPO activity in the traumatized hemisphere was demonstrated at 24 and 48 h in both the WD (0.3152 ± 0.0472 and 0.3017 ± 0.0228 U/g, respectively, p < 0.05 vs controls) and CCI (0.1866 ± 0.0225 and 0.1937 ± 0.0772 U/g, respectively, p < 0.05 vs controls) models. MPO activity was below the sensitivity of the assay in the control, 2 h, and 168 h groups in both models. MPO activity at 24 h after CCI increased with the depth of injury (0.1866 ± 0.0225 vs 0.3011 ± 0.0141 U/g, 2.5 vs 3.0 mm depth, respectively, p < 0.05). Lesion volume at 2 weeks after WD trauma was 16.0 ± 2.7 mm3,17.5% larger than lesion volume after CCI (previously published data), but the difference between groups was not statistically significant. These data indicate that (1) MPO activity after traumatic brain injury is increased at 24 and 48 h and resolves by 168 h in both the WD and CCI models, and (2) MPO activity in the CCI model increases with the severity of trauma.