Fig. 1

Study procedure and grouping. In the first part of the experiment, we confirmed that repeated low-dose LPS i.p. injection could induce immune tolerance of PBM without inflammation or dopaminergic neuronal loss in the brain. To induct endotoxic tolerance, rats were pre-treated with repeated 0.3 mg/kg LPS intraperitoneal injection for 4 days. Then, PBM were isolated, cultured, and restimulated by a hige-dose LPS. Moreover, we verified that peripheral repeated low-dose LPS intraperitoneal administration was failing to cause inflammation or dopaminergic neuronal loss in the brain parenchyma of rats. According to the different preconditioning, three groups were involved: the control group (n = 15), the PBS (i.p.) group (n = 6), and the LPS (i.p.) group (n = 42). In the second part of the experiment, we investigated the neuroprotective role of peripheral immune tolerance in intracranial LPS injection-induced neuroinflammation-related neurodegeneration. Neuroinflammation-induced PD rat model was conducted by 15 μg LPS intracranial injection into the right striatum. Inflammatory cytokines, microglial activation, loss of dopaminergic neurons, as well the behavior impairment were detected at indicated time points. Four groups were involved, including a control group without treatment, a PBS(striatum) group with striatal PBS injection as the sham group, a PBS (i.p.) + LPS (striatum) group with peripheral PBS pre-treatment prior to striatal 15 μg LPS injection, and a LPS (i.p.) + LPS (striatum) group with peripheral LPS pre-treatment prior to striatal 15 μg LPS injection