Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 6, Issue 256, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.3009430
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Funding
- Japan Society for the Promotion of Science Fellows, Scientific Research on Innovative Areas (Comprehensive Brain Science Network and Foundation of Synapse and Neurocircuit Pathology)
- Challenging Exploratory Research from the Ministry of Education, Science, Sports and Culture of Japan
- Research Foundations from the General Insurance Association of Japan
- Grants-in-Aid for Scientific Research [26861198, 14J01375, 25460721] Funding Source: KAKEN
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Spinal cord injury (SCI) is a devastating disorder for which the identification of exacerbating factors is urgently needed. We demonstrate that transient hyperglycemia during acute SCI is a detrimental factor that impairs functional improvement in mice and human patients after acute SCI. Under hyperglycemic conditions, both in vivo and in vitro, inflammation was enhanced through promotion of the nuclear translocation of the nuclear factor kappa B (NF-kappa B) transcription factor in microglial cells. During acute SCI, hyperglycemic mice exhibited progressive neural damage, with more severe motor deficits than those observed in normoglycemic mice. Consistent with the animal study findings, a Pearson chi(2) analysis of data for 528 patients with SCI indicated that hyperglycemia on admission (glucose concentration >= 126 mg/dl) was a significant risk predictor of poor functional outcome. Moreover, a multiple linear regression analysis showed hyperglycemia at admission to be a powerful independent risk factor for a poor motor outcome, even after excluding patients with diabetes mellitus with chronic hyperglycemia (regression coefficient, -1.37; 95% confidence interval, -2.65 to -0.10; P < 0.05). Manipulating blood glucose during acute SCI in hyperglycemic mice rescued the exacerbation of pathophysiology and improved motor functional outcomes. Our findings suggest that hyperglycemia during acute SCI may be a useful prognostic factor with a negative impact on motor function, highlighting the importance of achieving tight glycemic control after central nervous system injury.
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