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Inhibiting High Mobility Group Box-1 Reduces Early Spinal Cord Edema and Attenuates Astrocyte Activation and Aquaporin-4 Expression after Spinal Cord Injury in Rats

Journal of neurotrauma, 2019-02, Vol.36 (3), p.421-435 [Peer Reviewed Journal]

Copyright 2019, Mary Ann Liebert, Inc., publishers ;ISSN: 0897-7151 ;EISSN: 1557-9042 ;DOI: 10.1089/neu.2018.5642 ;PMID: 29929431

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Title:
Inhibiting High Mobility Group Box-1 Reduces Early Spinal Cord Edema and Attenuates Astrocyte Activation and Aquaporin-4 Expression after Spinal Cord Injury in Rats
Author: Sun, Lin ; Li, Man ; Ma, Xun ; Zhang, Li ; Song, Junlai ; Lv, Cong ; He, Yajun
Subjects: Animals ; Aquaporin 4 ; Aquaporin 4 - metabolism ; Aquaporins ; Astrocytes - metabolism ; Cytokines ; Cytotoxicity ; Deoxyribonucleic acid ; Disease Models, Animal ; DNA ; Edema ; Edema - drug therapy ; Edema - etiology ; Edema - metabolism ; Female ; Glial fibrillary acidic protein ; Glial Fibrillary Acidic Protein - metabolism ; Glycyrrhizic Acid - pharmacology ; Glycyrrhizin ; HMGB1 protein ; HMGB1 Protein - antagonists & inhibitors ; Hospitals ; Inflammation ; Kinases ; Laboratory animals ; Laminectomy ; Mobility ; NF-kappa B - metabolism ; NF-κB protein ; Orthopedics ; Proteins ; Pyruvates - pharmacology ; Pyruvic acid ; Rats ; Rats, Sprague-Dawley ; Rodents ; Signal transduction ; Spinal Cord - drug effects ; Spinal Cord - metabolism ; Spinal cord injuries ; Spinal Cord Injuries - complications ; Spinal Cord Injuries - metabolism ; Spinal cord injury ; Studies ; TLR4 protein ; Toll-like receptors ; Transcription factors ; Water content
Is Part Of: Journal of neurotrauma, 2019-02, Vol.36 (3), p.421-435
Description: High mobility group box-1 (HMGB1) could function as an early trigger for pro-inflammatory activation after spinal cord injury (SCI). Spinal cord edema contributes to inflammatory response mechanisms and a poor clinical prognosis after SCI, for which efficient therapies targeting the specific molecules involved remain limited. This study was designed to evaluate the roles of HMGB1 on the regulation of early spinal cord edema, astrocyte activation, and aquaporin-4 (AQP4) expression in a rat SCI model. Adult female Sprague-Dawley rats underwent laminectomy at T10, and the SCI model was induced by a heavy falling object. After SCI, rats received ethyl pyruvate (EP) or glycyrrhizin (GL) via an intraperitoneal injection to inhibit HMGB1. The effects of HMGB1 inhibition on the early spinal cord edema, astrocyte activation (glial fibrillary acidic protein [GFAP] expression), and AQP4 expression after SCI (12 h-3 days) were analyzed. The results showed that EP or GL effectively inhibited HMGB1 expression in the spinal cord and HMGB1 levels in the serum of SCI rats. HMGB1 inhibition improved motor function, reduced spinal cord water content, and attenuated spinal cord edema in SCI rats. HMGB1 inhibition decreased SCI-associated GFAP and AQP4 overexpression in the spinal cord. Further, HMGB1 inhibition also repressed the activation of the toll-like receptor 4/myeloid differentiation primary response gene 88/nuclear factor-kappa B signaling pathway. These results implicate that HMGB1 inhibition improved locomotor function and reduced early spinal cord edema, which was associated with a downregulation of astrocyte activation (GFAP expression) and AQP4 expression in SCI rats.
Publisher: United States: Mary Ann Liebert, Inc
Language: English
Identifier: ISSN: 0897-7151
EISSN: 1557-9042
DOI: 10.1089/neu.2018.5642
PMID: 29929431
Source: ProQuest One Psychology
AUTh Library subscriptions: ProQuest Central
MEDLINE
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Inhibiting High Mobility Group Box-1 Reduces Early Spinal Cord Edema and Attenuates Astrocyte Activation and Aquaporin-4 Expression after Spinal Cord Injury in Rats

Copyright 2019, Mary Ann Liebert, Inc., publishers ;ISSN: 0897-7151 ;EISSN: 1557-9042 ;DOI: 10.1089/neu.2018.5642 ;PMID: 29929431

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