Anti-high mobility group box-1 (HMGB1) antibody therapy for spinal cord ischemia-reperfusion injury in rabbits

• Published in: Proceedings for Annual Meeting of The Japanese Pharmacological Society Vol. 94; p. 3-Y-F2-1
• Main Authors: Genya, Muraoka, Liu, Keyue, Qiao, Handong, Ousaka, Daiki, Wang, Dengli, Fujii, Yasuhiro, Kasahara, Shingo, Nishibori, Masahiro
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Pharmacological Society 2021
• ISSN: 2435-4953; 2435-4953
• DOI: 10.1254/jpssuppl.94.0_3-Y-F2-1

IntroductionSpinal cord ischemia and reperfusion (I/R) injury is one of the most devastating complications after thoracic and thoracoabdominal aortic aneurysm surgery. Several studies showed that levels of HMGB1 in serum were increased in patients who suffered from spinal cord I/R injury. These data strongly suggest that HMGB1 may play a crucial role in spinal cord I/R injury.Materials and MethodsMale New Zealand white rabbits were used for the experiments. The abdominal aorta at the level of the left renal artery was exposed, and, after heparinization, occluded for 11 minutes. The rabbits were intravenously administered an anti-HMGB1 mAb (#10-22, 2mg/kg) or class-matched control IgG (anti-keyhole limpet hemocyanin mAb) twice immediately and 6h after reperfusion. The neurological findings were assessed at 6, 24 and 48 hours after reperfusion. At 48hr after reperfusion, the rabbits were sacrificed to obtain the specimen of spinal cord and blood samples.ResultsAdministration of anti-HMGB1 mAb ameliorated the intensity of spinal cord infarction and preserved the number of motor neuron cells, in association with decreased activated microglia and astrocyte. Consequently, anti-HMGB1 mAb significantly improved the neurological outcomes after spinal I/R injury in rabbits.  These results strongly indicate that HMGB1 plays a critical role in the development of spinal cord I/R induced secondary injury through the amplification of inflammatory response. ConclusionIntravenous injection of neutralizing anti-HMGB1 mAb has potential as a novel therapeutic strategy for spinal cord I/R injury.