Inhibiting High-Mobility Group Box 1 (HMGB1) Attenuates Inflammatory Cytokine Expression and Neurological Deficit in Isc
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ORIGINAL ARTICLE
Inhibiting High-Mobility Group Box 1 (HMGB1) Attenuates Inflammatory Cytokine Expression and Neurological Deficit in Ischemic Brain Injury Following Cardiac Arrest in Rats Mei Xu,1 Gui-ming Zhou,2 Li-hua Wang,3 Li Zhu,2 Jin-mei Liu,2 Xiao-dong Wang,4 Hong-tao Li,4,6 and Lei Chen5,6
ABSTRACT—Cardiac arrest (CA), if untreated for more than 5 min, can induce severe brain damage, the underlying mechanism of which is still unclear. Previous studies have indicated that high-mobility group box 1 (HMGB1), a nuclear protein implicated in several inflammatory disorders, is involved in the inflammatory processes following brain ischemia. However, the role of HMGB1 in brain dysfunction after CA is yet to be determined. In a rat CA model, HMGB1 protein expression was higher at 1, 3, and 7 days post-CA, compared to that in naïve and sham-treated rats. Following injection of HMGB1 antibody (anti-HMGB1) into the cerebral ventricles, neurological deficit scores were significantly decreased in the CA group as compared to that in the naïve and sham group. Nissl staining showed significant neuronal loss in the hippocampal CA1 region following CA, which was significantly attenuated by anti-HMGB1-treatment (10 and 50 μg) in comparison with the vehicle-injected control. CA induced a significant increase in the levels of the cytokine interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in the hippocampus as revealed by real-time polymerase chain reaction and enzymelinked immunosorbent assay. Treatment with anti-HMGB1 significantly inhibited IL-1β and TNF-α expression. Our study suggests that HMGB1 contributes significantly to CA-induced brain dysfunction and that inhibiting HMGB1 function and expression may be an effective therapeutic approach to CAinduced ischemic brain injury. KEY WORDS: cardiac arrest; resuscitation; high-mobility group box 1; hippocampus; neurological deficit.
INTRODUCTION
Mei Xu, Gui-ming Zhou and Li-hua Wang contributed equally to this work. 1
Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin, 300052, China 2 Department of Ultrasound, Tianjin Medical University General Hospital, Tianjin, 300052, China 3 Department of Cardiothoracic Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China 4 Department of Endocrinology, Tianjin Corps Hospital of Chinese People’s Armed Police Forces, Tianjin, 300252, China 5 Department of Ultrasound, Tianjin Corps Hospital of Chinese People’s Armed Police Forces, Tianjin, 300252, China 6 To whom correspondence should be addressed to Hong-tao Li at Department of Endocrinology, Tianjin Corps Hospital of Chinese People’s Armed Police Forces, Tianjin, 300252, China. E-mail: [email protected]; and Lei Chen at Department of Ultrasound, Tianjin Corps Hospital of Chinese People’s Armed Police Forces, Tianjin, 300252, China. E-mail: [email protected]
Cardiac arrest (CA) affects millions of people worldwide every year. After successful cardiopulmonary resuscitation, survivors of CA often show evidence of neuronal injury an
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