title: Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans.
abstract: 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 κB (NF-κB) 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 χ(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.
authors.affiliation: Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kazu
authors.initials: K
authors.lastname: Kobayakawa
authors.affiliation: Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumamaru
authors.affiliation: Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Saiwai
authors.affiliation: Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohkawa
authors.affiliation: Department of Medical Informatics, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kishimoto
authors.affiliation: Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yokota
authors.affiliation: Department of Rehabilitation, Spinal Injuries Center, Izuka 820-8508, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Ideta
authors.affiliation: Department of Orthopaedic Surgery, Spinal Injuries Center, Izuka 820-8508, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Shiba
authors.affiliation: Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tozaki-Saitoh
authors.affiliation: Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. seokada@ortho.med.kyushu-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
mesh_terms: D000208:Acute Disease; D000368:Aged; D000818:Animals; D017209:Apoptosis; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*
chemical_list: D016328:NF-kappa B