Inhibiting Histamine H3 Receptor Enhanced Autophagy Protect Against Inflammatory Response In Early Brain Injury Following A Mice Subarachnoid Hemorrhage

ObjectInhibiting histamine H3R receptor has beneficial effects in CNS,however,the molecular mechanisms underlying effects in SAH have not been clearly identified.This study was undertaken to determine influence of H3R and the possible mechanisms of these effects in early brain injury following subarachnoid hemorrhage.Methods72 C57BL/6J mice were randomly divided into sham+vehicle group,SAH+Thioperamide group,another 24 H3R K.O.mice formed the SAH+H3R K.O.group.The SAH model was induced by endovascular perforation.24 h after SAH,the amount of brain water content,and expression of cerebral caspase-1,cleaved IL-1β,IL-18,Beclin-1,LC3,ZO-1,occluding and claudin-5 in all groups were assayed.SAH grades and neurological scores were recorded after 24 h of SAH.ResultsCompared with the sham+vehicle group,the expression of Beclin-1,LC3,IL-1,IL-18,cleaved,IL-1,caspase-1,SAH,ZO-1,Occludin and Claudin-5 were significantly decreased in the cortex after cerebral cortex infarction.Blood brain barrier permeability and brain edema and neurological function was significantly increased(P<0.05);compared with group SAH+vehicle,Thio and H3R knockout mice Beclin-1 in the cerebral cortex,the expression of LC3 further increased significantly,IL-1 beta,IL-18 cleaved,IL-1 beta,decreased the expression of Caspase-1,ZO-1,Occludin and Claudin-5 expression increased and the blood brain barrier damage and brain edema and neurological improvement(P<0.05).ConclusionOur work demonstrated that inhibiting H3R induce autophagy protects against the inflammatory response in early brain injury following SAH.Thioperamide treatment may have important clinical potentials for management of S AH.