Background and aims: Neuroprotective therapies are needed to improve the outcomes following ischemic brain injury from cardiac arrest in children. Previously we showed a monoclonal antibody to CD18 (aCD18ab) injected following injury blocks cerebral and systemic inflammation and improves neuronal survival and spatial memory in a 2 vessel occlusion (2VO) model of forebrain ischemia in juvenile mice. Aims: To discover serum biomarkers of cerebral ischemia and neuroprotection. Methods: This study was conducted in strict accordance with the Hospital for Sick Children and the University of Ottawa Animal Care Committees, and Canadian Council of Animal Care guidelines. Mice were randomized to 3 groups: 1) 2VO injected with 2 mg/kg aCD18ab; 2) 2VO injected with control antibody and; 3) sham. We included 10 mice in each of the 3 groups. Serum samples were taken at 24 hours following injury or sham operation and low abundance proteins were identified using tandem mass spectrometry. Results: More than 400 serum peptides were identified by mass spectrometry. Serum kallikrein-1 was significantly differentially expressed in the three groups. There was a 7 to 56 fold increase in the mice subject to 2VO and treated with a control antibody compared to sham, and a 98 to 505 fold increase in the mice subject to 2VO and treated with aCD18ab compared to sham. Conclusions: Our results suggesting kallikrein-1 may be an important biomarker of neuroprotection which could be used in pilot randomized controlled trials of this neuroprotective therapy in children with cardiac arrest.
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