Title |
Hypothermia inhibits the propagation of acute ischemic injury by inhibiting HMGB1
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Published in |
Molecular Brain, August 2016
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DOI | 10.1186/s13041-016-0260-0 |
Pubmed ID | |
Authors |
Jung Ho Lee, Eun Jang Yoon, Jeho Seo, Adriana Kavoussi, Yong Eun Chung, Sung Phil Chung, Incheol Park, Chul Hoon Kim, Je Sung You |
Abstract |
Acute ischemic stroke causes significant chronic disability worldwide. We designed this study to clarify the mechanism by which hypothermia helps alleviate acute ischemic stroke. In a middle cerebral artery occlusion model (4 h ischemia without reperfusion), hypothermia effectively reduces mean infarct volume. Hypothermia also prevents neurons in the infarct area from releasing high mobility group box 1 (HMGB1), the most well-studied damage-associated molecular pattern protein. By preventing its release, hypothermia also prevents the typical middle cerebral artery occlusion-induced increase in serum HMGB1. We also found that both glycyrrhizin-mediated inhibition of HMGB1 and intracerebroventricular neutralizing antibody treatments before middle cerebral artery occlusion onset diminish infarct volume. This suggests a clear neuroprotective effect of HMGB1 inhibition by hypothermia in the brain. We next used real-time polymerase chain reaction to measure the levels of pro-inflammatory cytokines in peri-infarct regions. Although middle cerebral artery occlusion increases the expression of interleukin-1β and tissue necrosis factor-α, this elevation is suppressed by both hypothermia and glycyrrhizin treatment. We show that hypothermia reduces the production of inflammatory cytokines and helps salvage peri-infarct regions from the propagation of ischemic injury via HMGB1 blockade. In addition to suggesting a potential mechanism for hypothermia's therapeutic effects, our results suggest HMGB1 modulation may lengthen the therapeutic window for stroke treatments. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 4 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 75% |
Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 4% |
Unknown | 27 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 5 | 18% |
Student > Ph. D. Student | 4 | 14% |
Professor > Associate Professor | 3 | 11% |
Student > Bachelor | 3 | 11% |
Student > Master | 2 | 7% |
Other | 2 | 7% |
Unknown | 9 | 32% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 4 | 14% |
Medicine and Dentistry | 4 | 14% |
Engineering | 3 | 11% |
Agricultural and Biological Sciences | 2 | 7% |
Neuroscience | 2 | 7% |
Other | 3 | 11% |
Unknown | 10 | 36% |