Impact of Toll-Like Receptor 2 Deficiency on Survival and Neurological Function after Cardiac Arrest: A Murine Model of Cardiopulmonary Resuscitation

• DOI: 10.1371/journal.pone.0074944
• Publication Date: 2013-09-16T17:17:05Z
• Authors: Stefan Bergt; Anne Güter; Andrea Grub; Nana-Maria Wagner; Claudia Beltschany; Sönke Langner; Andreas Wree; Steve Hildebrandt; Gabriele Nöldge-S...; Brigitte Vollmar; Jan P. Roesner
• Keywords: Science; Q; R; Cardiopulmonary Resuscitation; Mice, Mutant Strains; Toll-Like Receptor 2; Heart Arrest; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Medicine; Animals; Female; Research Article

Cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR) is associated with poor survival rate and neurofunctional outcome. Toll-like receptor 2 (TLR2) plays an important role in conditions of sterile inflammation such as reperfusion injury. Recent data demonstrated beneficial effects the administration TLR2-blocking antibodies ischemia/reperfusion In this study we investigated TLR2 for outcome after CA/CPR mice.Female TLR2-deficient (TLR2(-/-)) wild type (WT) mice were subjected to CA eight min induced intravenous injection potassium chloride CPR external chest compression. Upon beginning CPR, n = 15 WT received 5 µg/g T2.5 inhibiting antibody intravenously while 30 TLR2(-/-) 31 controls normal saline. Survival neurological evaluated during a 28-day follow up period. Basic function, balance, coordination overall motor function well spatial learning memory investigated, respectively. separate set experiments, six per group analysed cytokine corticosterone serum levels hours CA/CPR.TLR2 deficiency treatment blocking increased (77% 80% vs. 51% control; both P < 0.05). Neurofunctional performance was less compromised treated mice. Compared mice, exhibited reduced IL-6 (both 0.05) but not IL-1β plasma concentrations 0.05).Deficiency or functional blockade improved mouse model CA/CPR. Thus, inhibition could provide novel therapeutic approach reducing mortality morbidity cardiac resuscitation.