Cerebral Alterations Following Experimental Multiple Trauma and Hemorrhagic Shock.

Abstract

Multiple trauma (MT) associated with hemorrhagic shock (HS) might lead to cerebral hypoperfusion and brain damage. We investigated cerebral alterations using a new porcine MT/HS model without traumatic brain injury (TBI) and assessed the neuroprotective properties of mild therapeutic hypothermia. Male pigs underwent standardized MT with HS (45% or 50% loss of blood volume) and resuscitation after 90/120 min (T90/T120). In additional groups (TH90/TH120) mild hypothermia (33°C) was induced following resuscitation. Normothermic or hypothermic sham animals served as controls. Intracranial pressure, cerebral perfusion pressure (CPP), and cerebral oxygenation (PtiO2) were recorded up to 48.5 h. Serum protein S-100B and neuron-specific enolase (NSE) were measured by ELISA. Cerebral inflammation was quantified on hematoxylin and eosin -stained brain slices; Iba1, S100, and inducible nitric oxide synthase (iNOS) expression was assessed using immunohistochemistry. Directly after MT/HS, CPP and PtiO2 were significantly lower in T90/T120 groups compared with sham. After resuscitation both parameters showed a gradual recovery. Serum protein S-100B and NSE increased temporarily as a result of MT/HS in T90 and T90/T120 groups, respectively. Cerebral inflammation was found in all groups. Iba1-staining showed significant microgliosis in T90 and T120 animals. iNOS-staining indicated a M1 polarization. Mild hypothermia reduced cerebral inflammation in the TH90 group, but resulted in increased iNOS activation. In this porcine long-term model, we did not find evidence of gross cerebral damage when resuscitation was initiated within 120 min after MT/HS without TBI. However, trauma-related microglia activation and M1 microglia polarization might be a consequence of temporary hypoxia/ischemia and further research is warranted to detail underlying mechanisms. Interestingly, mild hypothermia did not exhibit neuroprotective properties when initiated in a delayed fashion.