Increased histamine by thioperamide exerts its neuronal protection effect through postsynaptic H1 receptor in neonatal hypoxic-ischemic encephalopathy rat model

Blocking histamine H3 receptor leads to increased histamine in the brain. The effects of H3 receptor antagonist in the rat model of neonatal hypoxic-ischemic encephalopathy (NHIE) and its mechanism is uncertain. In our study, we employed a NHIE model of postnatal 7 days rats and tested the brain water content, hippocampal histamine, cerebral MDA and SOD levels under the different combinations of H1, H2 and H3 antagnonists in order to investigate the effect of H3 antagonist and its mechanism in the NHIE model. H3 antagonist thioperamide decreased the brain water content and MDA and increased the hippocampal histamine and SOD level; H1 antagonist pyrilamine reversed the effects of thioperamide in the H3+H1 group, however, H2 antagonist has no significant influence on the effects of thioperamide as their combinational use. We deduce that thioperamide plays a neuronal protective role by increasing brain histamine through postsynaptic H1 receptor in the NHIE model.