Differential roles of TLR2 and TLR4 in acute focal cerebral ischemia/reperfusion injury in mice

Recent studies have shown that Toll-like receptors (TLRs) are involved in cerebral ischemia/reperfusion (I/R) injury. This study was to investigate the role of TLR2 and TLR4 in acute focal cerebral I/R injury. Cerebral infarct size, neurological function and mortality were evaluated. NF kappa B binding activity, phosphorylation of IKB alpha, Akt and ERK1/2 were examined in ischemic cerebral tissue by EMSA and Western blots. Compared to wild type (WT) mice, in TLR4 knockout (TLR4KO) mice, brain infarct size was decreased (2.6 +/- 1.18% vs 11.6 +/- 1.97% of whole cerebral volume, p<0.05) and neurological function was maintained (7.3 +/- 0.79 vs 4.7 +/- 0.68, p<0.05). However, compared to TLR4KO mice, TLR2 knockout (TLR2KO) mice showed higher mortality (38.2% vs 13.0%, p<0.05), decreased neurological function (2.9 +/- 0.53 vs 7.3 +/- 0.79, p<0.05) and increased brain infarct size (19.1 +/- 1.33% vs 2.6 +/- 1.18%, p<0.05). NF kappa B activation and I kappa B alpha phosphorylation were attenuated in TLR4KO mice (1.09 +/- 0.02 and 1.2 +/- 0.04) compared to TLR2KO mice (1.31 +/- 0.02 and 2.2 +/- 0.32) after cerebral ischemia. Compared to TLR4KO mice, in TLR2KO mice, the phosphorylation of Akt (0.2 +/- 0.03 vs 0.9 +/- 0.16, p<0.05) and ERK1/2 (0.8 +/- 0.06 vs 1.3 +/- 0.17) evoked by cerebral I/R was attenuated. The present study demonstrates that TLR2 and TLR4 play differential roles in acute cerebral I/R injury. Specifically, TLR4 contributes to cerebral I/R injury, while TLR2 appears to be neuroprotective by enhancing the activation of protective signaling in response to cerebral I/R. (C) 2009 Elsevier B.V. All rights reserved.