Pivotal neuroinflammatory and therapeutic role of high mobility group box 1 in ischemic stroke
Open Access
- 5 December 2017
- journal article
- review article
- Published by Portland Press Ltd. in Bioscience Reports
- Vol. 37 (6)
- https://doi.org/10.1042/bsr20171104
Abstract
Stroke is a major cause of mortality and disability worldwide. Stroke is a frequent and severe neurovascular disorder. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, prevention and treatment of stroke are crucial issues in humans. High mobility group box 1 (HMGB1) is non-histone nuclear protein that is currently one of the crucial proinflammatory alarmins in ischemic stroke (IS). It is instantly released from necrotic cells in the ischemic core and activates an early inflammatory response. HMGB1 may signal via its putative receptors, such as receptor for advanced glycation end products (RAGE), toll-like receptors (TLRs) as well as matrix metalloproteinase (MMP) enzymes during IS. These receptors are expressed in brain cells. Additionally, brain-released HMGB1 can be redox modified in the circulation and activate peripheral immune cells. The role of HMGB1 may be more complex. HMGB1 possesses beneficial actions, such as endothelial activation, enhancement of neurite outgrowth, and neuronal survival. HMGB1 may also provide a novel link for brain-immune communication leading to post-stroke immunomodulation. Therefore, HMGB1 is new promising therapeutic intervention aimed at promoting neurovascular repair and remodeling after stroke. In this review, we look at the mechanisms of secretion of HMGB1, the role of receptors, MMP enzymes, hypoglycemia, atherosclerosis, edema, angiogenesis as well as neuroimmunological reactions and post-ischemic brain recovery in IS. We also outline therapeutic roles of HMGB1 in IS.Keywords
This publication has 122 references indexed in Scilit:
- Intranasal Delivery of HMGB1 siRNA Confers Target Gene Knockdown and Robust Neuroprotection in the Postischemic BrainMolecular Therapy, 2012
- Niaspan reduces high-mobility group box 1/receptor for advanced glycation endproducts after stroke in type-1 diabetic ratsNeuroscience, 2011
- Toll-like receptors 2 and 4 in ischemic stroke: Outcome and therapeutic valuesJournal of Cerebral Blood Flow & Metabolism, 2011
- HMBG1 Mediates Ischemia—Reperfusion Injury by TRIF-Adaptor Independent Toll-Like Receptor 4 SignalingJournal of Cerebral Blood Flow & Metabolism, 2010
- TIMP-3 and MMP-3 contribute to delayed inflammation and hippocampal neuronal death following global ischemiaExperimental Neurology, 2009
- Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemiaNeuroscience, 2009
- Potential utility of aquaporin modulators for therapy of brain disordersProgress in Brain Research, 2008
- Induction of Immunological Tolerance by Apoptotic Cells Requires Caspase-Dependent Oxidation of High-Mobility Group Box-1 ProteinImmunity, 2008
- Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficitsProceedings of the National Academy of Sciences of the United States of America, 2007
- RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brainNature Medicine, 2003