Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans

被引：65

作者：

Kobayakawa, Kazu ^{[1
,2
]}

Kumamaru, Hiromi ^{[1
,2
]}

Saiwai, Hirokazu ^{[1
,2
]}

Kubota, Kensuke ^{[1
,2
]}

Ohkawa, Yasuyuki ^{[1
]}

Kishimoto, Junji ^{[3
]}

Yokota, Kazuya ^{[1
,2
]}

Ideta, Ryosuke ^{[4
]}

Shiba, Keiichiro ^{[5
]}

Tozaki-Saitoh, Hidetoshi ^{[6
]}

Inoue, Kazuhide ^{[6
]}

Iwamoto, Yukihide ^{[2
]}

Okada, Seiji ^{[1
,2
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Dept Adv Med Initiat, Fukuoka 8128582, Japan

[2] Kyushu Univ, Grad Sch Med Sci, Dept Orthoped Surg, Fukuoka 8128582, Japan

[3] Kyushu Univ, Dept Med Informat, Fukuoka 8128582, Japan

[4] Spinal Injuries Ctr, Dept Rehabil, Izuka 8208508, Japan

[5] Spinal Injuries Ctr, Dept Orthopaed Surg, Izuka 8208508, Japan

[6] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Mol & Syst Pharmacol, Fukuoka 8128582, Japan

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2014年 / 6卷 / 256期

基金：

日本学术振兴会;

关键词：

NF-KAPPA-B; INSULIN THERAPY; DIABETIC MICE; ACTIVATION; GLUCOSE; METHYLPREDNISOLONE; INFLAMMATION; COMPLICATIONS; MACROPHAGES; DYSFUNCTION;

D O I：

10.1126/scitranslmed.3009430

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：14