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Fig. 6 | Journal of Neuroinflammation

Fig. 6

From: Role of non-macrophage cell-derived HMGB1 in oxaliplatin-induced peripheral neuropathy and its prevention by the thrombin/thrombomodulin system in rodents: negative impact of anticoagulants

Fig. 6

Hypothetical scheme for a causative role of HMGB1 in oxaliplatin-induced peripheral neuropathy and for thrombin-dependent anti-neuropathic effects of exogenously applied TMα and endogenous TM expressed in the endothelium. Oxaliplatin releases HMGB1 mainly from non-macrophage cells, which causes peripheral neuropathy via activation of TLR4, RAGE, and CXCL12/CXCR4 signaling, but not TLR5. Exogenously applied TMα and endothelial TM prevent oxaliplatin-induced neuropathy by promoting thrombin-dependent degradation of HMGB1. Anticoagulants, such as argatroban, dabigatran, warfarin, and rivaroxaban, cancel the anti-neuropathic activity of TMα and endothelial TM

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Journal of Neuroinflammation

ISSN: 1742-2094