ABSTRACT
As part of the acute inflammatory response, neutrophils accumulate in the central nervous system after injury. Recently, a soluble human recombinant complement receptor (sCR1; BRL 55730; T Cell Sciences, Inc., Cambridge, MA, U.S.A.) has been developed that inhibits the activation of both the classical and the alternative pathways of complement. sCR1 attenuates the effects of the acute inflammatory response in several models of injury outside the central nervous system. The role of complement in traumatic brain injury, however, remains undefined. We hypothesized that treatment with sCR1 would attenuate neutrophil accumulation in the brain after cerebral trauma. Using a randomized, blinded protocol, 18 anesthetized Sprague-Dawley rats were pre-treated with sCR1 or saline (control) at both 2 h and 2 min before trauma (weight drop) to the exposed right parietal cortex. A third dose of sCR1 (or saline) was given 6 h after trauma. Coronal brain sections centered on the site of trauma were obtained at 24 h after trauma and analyzed for myeloperoxidase (MPO) activity as a marker of neutrophil accumulation. Complete blood counts with differential were obtained before treatment with sCR1 and at 24 h after trauma. At 24 h after trauma, brain MPO activity was reduced by 41% in sCR1-treated rats compared with control rats [0.1599 +/- 0.102 versus 0.2712 +/- 0.178 U/g (mean +/- SD); p = 0.02]. The neutrophil count in peripheral blood increased approximately twofold in both groups. Neutrophil accumulation occurring in the brain after trauma is inhibited by sCR1 treatment. This suggests that complement activation is involved in the local inflammatory response to traumatic brain injury and plays an important role in neutrophil accumulation in the injured brain.
Subject(s)
Brain Injuries/pathology , Complement C1/metabolism , Neutrophils/pathology , Receptors, Complement/physiology , Animals , Blood/metabolism , Brain/metabolism , Leukocyte Count , Male , Peroxidase/metabolism , Rats , Rats, Sprague-Dawley , SolubilityABSTRACT
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.(ABSTRACT TRUNCATED AT 250 WORDS)
