Expression of HMGB1 in Organs in a Rodent Model of Transient Ischemia

Abstract

Background: High mobility group box 1 (HMGB1) is a chromatin structural protein expressed ubiquitously inthe nuclei of mammalian cells. Increasing evidence suggests that inflammatory responses are involved in the progression of systemic injuries induced by a diverse range of insults, including stroke, trauma, tumors, and degenerative diseases. Whether HMGB1 expression in systemic organs is associated with transient ischemic attack (TIA)remains unclear. We hypothesized that HMGB1 expression after TIA would exacerbate systemic symptoms due toacute inflammation.Material and Methods: We performed transient bilateral and unilateral common carotid artery occlusion (2VOand 1VO) on Sprague‒Dawley (SD) male rats. Rats were randomized to the sham, 1VO, and 2VO groups. Thesham group underwent no procedure that involved common carotid artery occlusion. Common carotid arterieswere clamped for 30 minutes and, subsequently, reperfused for 24 hours. Brain, heart, liver, lung, spleen, kidneyand intestine tissue samples were collected for biochemical and histopathological analysis. Protein and mRNA expression were determined by western blot analysis and polymerase chain reaction (PCR).Results: HMGB1 expression increased in the brain, liver, spleen and intestine of the rat 1VO and 2VO models.In vivo results indicated high expression of HMGB1 in TIA, and the expression of MMP-9 and PKCδ in the cerebral cortex and hippocampus was regulated by HMGB1. In the 2VO model, the expression of CD11b and GFAPin the cerebral cortex was significantly increased compared with that in the control group (P < 0.001). HMGB1was translocated from the nucleus to the cytoplasm at early stages after TIA and then localized to the cytoplasm ofphagocytic microglia at later stages.Conclusion: HMGB1 expression increased in the systemic organs after TIA. HMGB1 promotes systemic inflammation, which mediates the immune response and tissue damage in the brain after TIA. Targeting HMGB1signaling may be a promising therapeutic approach for the treatment of TIA.