High-mobility group box1 protein promotes neuroinflammation after intracerebral hemorrhage in rats

Lei, Chunyan; Su, Lin; Zhang, C; Tao, Wendan; Dong, Wei; Zeng, Hao; Liu, M.; Wu, Bo

doi:10.1016/j.neuroscience.2012.10.023

Cited by 55 publications

(45 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7,18,19 In previous work, we showed that HMGB1 is released into the cytoplasm during the acute phase after ICH, which resulted in neuronal apoptosis, cerebral edema, and neurological impairment. 7 Taken together, these results suggest that HMGB1 acts as an early proinflammatory cytokine within the neurovascular unit to mediate inflammation during the acute phase of ICH.…”

Section: Discussionmentioning

confidence: 98%

Activation of the High-Mobility Group Box 1 Protein-Receptor for Advanced Glycation End-Products Signaling Pathway in Rats During Neurogenesis After Intracerebral Hemorrhage

Lei

Cao

et al. 2015

Stroke

View full text Add to dashboard Cite

500I ntracerebral hemorrhage (ICH) accounts for roughly 15% of all strokes and is associated with mortality rates approaching 50%; survivors are often left with serious disability.1 The brain responds to ICH in complex ways that involve pathophysiological responses, such as excitotoxicity, free radical damage, and inflammation. Moreover, the brain initiates remodeling processes, such as neurogenesis, angiogenesis, and synaptic plasticity, designed to restore neurological function after ICH.2-4 As part of this neurogenesis, precursor cells in the subventricular and subgranular zones of the hippocampus migrate into injured brain areas, where they differentiate into mature neurons and glia. [4][5][6] High-mobility group box 1 (HMGB1), a highly conserved nonhistone nuclear DNA-binding protein, is passively released by necrotic cells or actively secreted by macrophages, myeloid dendritic cells, and natural killer cells. 7-9Immediately after ICH, HMGB1 serves as an alarmin or damage-associated molecular signal that mediates cross-talk between damaged and healthy cells and triggers an inflammatory response.7-9 At later times after ICH, however, HMGB1 may promote neurogenesis that supports recovery of neuronal function. HMGB1 has been shown to increase neurite outgrowth in cultures and to promote neurovascular remodeling in cerebral ischemia in mice.10 However, the involvement Background and Purpose-Following intracerebral hemorrhage (ICH), high-mobility group box 1 protein (HMGB1) may promote neurogenesis that supports functional recovery. How HMGB1 regulates or participates in this process is unclear, as are the pattern recognition receptors and signaling pathways involved. Methods-ICH was induced by injection of collagenase in Sprague-Dawley rats, which were treated 3 days later with saline, with the HMGB1 inhibitor ethyl pyruvate or with FPS-ZM1, an antagonist of the receptor for advanced glycation end-products. A Sham group was treated with saline solution instead of collagenase and then treated 3 days later with saline again or with ethyl pyruvate or N-benzyl-4-chloro-N-cyclohexylbenzamide (FPS-ZM1). Expression of the following proteins was measured by Western blot, immunohistochemistry, or immunofluorescence: HMGB1, receptor for advanced glycation end-products, toll-like receptor (TLR)-2, TLR4, brain-derived neurotrophic factor, and matrix metalloproteinase-9. The number of cells positive for 5-bromo-2-deoxyuridine or doublecortin was determined by immunohistochemistry and immunofluorescence. Results-Levels of HMGB1, receptor for advanced glycation end-products, TLR4, TLR2, brain-derived neurotrophic factor, and matrix metalloproteinase-9 were significantly higher 14 days after ICH than at baseline, as were the numbers of 5-bromo-2-deoxyuridine-or doublecortin-positive cells. At the same time, HMGB1 moved from the nucleus into the cytoplasm. Administering ethyl pyruvate significantly reduced all these ICH-induced increases, except the increase in TLR4 and TLR2. Administering FPS-ZM1 reduced the ICH-induced increa...

show abstract

Section: Discussionmentioning

confidence: 98%

Activation of the High-Mobility Group Box 1 Protein-Receptor for Advanced Glycation End-Products Signaling Pathway in Rats During Neurogenesis After Intracerebral Hemorrhage

Lei

Cao

et al. 2015

Stroke

View full text Add to dashboard Cite

show abstract

“…Immunoblotting was performed on ipsilateral striatum homogenates as described (Lei et al, 2013b) (n = 7 from each group). Equal amounts of protein were subjected to 10-12% SDS-polyacrylamide gel electrophoresis and transferred onto polyvinylidene difluoride (PVDF) membranes (Millipore, Boston, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

HMGB1 may act via RAGE to promote angiogenesis in the later phase after intracerebral hemorrhage

et al. 2015

Self Cite

View full text Add to dashboard Cite

“…Elevated HMGB1 was found early at 2-4 h in ischemia-reperfused brains [75,82]. HMGB1 promoted neuroinflammation in rats with intracerebral hemorrhage (ICH) [83]. Antibody against HMGB1 reduced BBB permeability and infarct volume in rodent cerebral ischemic models [82].…”

Section: Mechanisms Of T-pa-induced Htmentioning

confidence: 99%

“…HMGB1 is closely related to oxidative stress, MMP activation and BBB disruption [13,83,84,96]. In ischemic stroke patients, an increased plasma HMGB1 level was correlated with MMP-9 level and poor clinical outcome [101].…”

Section: Mechanisms Of T-pa-induced Htmentioning

confidence: 99%

Targeting ONOO<sup>-</sup>/HMGB1/MMP-9 Signaling Cascades: Potential for Drug Development from Chinese Medicine to Attenuate Ischemic Brain Injury and Hemorrhagic Transformation Induced by Thrombolytic Treatment

Chen¹,

Guan²,

Shen³

2016

Integr Med Int

View full text Add to dashboard Cite

Stroke is the leading cause of death and disability worldwide, and ischemic stroke accounts for more than 85% of the stroke incidence. Tissue plasminogen activator (t-PA) is the only FDA-approved drug for ischemic stroke treatment with a narrow treatment time window of 4.5 h. Hemorrhagic transformation (HT) is a severe complication of delayed t-PA treatment in ischemic stroke. Thus, it is critically important to develop combination therapies to reduce HT and extend the therapeutic time window of t-PA. Current progress suggests that peroxynitrite (ONOO^-)/high-mobility group box 1 protein (HMGB1)/matrix metalloproteinase-9 (MMP-9) signaling cascades could be important for attenuating HT during thrombolytic treatment for acute ischemic stroke. Recently, important progress has been made in seeking for natural compounds from Chinese medicine for reducing ischemic stroke injury, with some of them targeting ONOO^-/HMGB1/MMP-9 signaling cascades. Herein, we analyze the roles and interactions of these three targets in mediating HT; subsequently, we summarize the potential compounds from Chinese herbal medicine for attenuating HT and analyze the related targets. Finally, we raise the potential issues to be addressed in further development of these compounds as combination therapy.

show abstract

High-mobility group box1 protein promotes neuroinflammation after intracerebral hemorrhage in rats

Cited by 55 publications

References 52 publications

Activation of the High-Mobility Group Box 1 Protein-Receptor for Advanced Glycation End-Products Signaling Pathway in Rats During Neurogenesis After Intracerebral Hemorrhage

Activation of the High-Mobility Group Box 1 Protein-Receptor for Advanced Glycation End-Products Signaling Pathway in Rats During Neurogenesis After Intracerebral Hemorrhage

HMGB1 may act via RAGE to promote angiogenesis in the later phase after intracerebral hemorrhage

Targeting ONOO<sup>-</sup>/HMGB1/MMP-9 Signaling Cascades: Potential for Drug Development from Chinese Medicine to Attenuate Ischemic Brain Injury and Hemorrhagic Transformation Induced by Thrombolytic Treatment

Contact Info

Product

Resources

About