Inflammatory mediators and blood brain barrier disruption in fatal brain edema of diabetic ketoacidosis

被引：78

作者：

Hoffman, William H. ^{[2
]}

Stamatovic, Svetlana M.

Andjelkovic, Anuska V. ^{[1
,3
]}

机构：

[1] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

[2] Med Coll Georgia, Dept Pediat, Sect Pediat Endocrinol, Augusta, GA 30912 USA

[3] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 USA

来源：

BRAIN RESEARCH | 2009年 / 1254卷

关键词：

Blood-brain barrier; Brain edema; CCL2; Diabetic ketoacidosis; Neuroinflammation; NF-kappa B; Nitrotyrosine; Oxidative stress; Tight junction protein; FACTOR-KAPPA-B; MICROVASCULAR ENDOTHELIAL-CELLS; GLYCATION END-PRODUCTS; NITRIC-OXIDE SYNTHASE; CEREBRAL EDEMA; COMPLEMENT ACTIVATION; LIPID-PEROXIDATION; OXIDATIVE STRESS; CHILDREN; EXPRESSION;

D O I：

10.1016/j.brainres.2008.11.100

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Brain edema (BE) is an uncommon but life-threatening complication of severe diabetic ketoacidosis (DKA) and its treatment. Despite advances in treatment of DKA, the pathogenesis of both initiation and progression of the associated BE is unclear. In the present study we examined the blood brain barrier (BBB) integrity and the potential involvement of the inflammatory mediators in BBB breakdown in two cases of fatal BE associated with DKA. in both cases there were typical signs of disruption of the BBB manifested by the absence of tight junction proteins (occludin, claudin-5, ZO-1 andJAM-1) in the parenchymal blood vessels, as well as albumin extravasation in examined brain areas. The neuroinflammatory markers chemokine CCL2, NF-kappa B and nitrotyrosine were localized in the perivascular areas of the disrupted BBB and diffusely distributed in the brain parenchyma. Our data indicate that neuroinflammation plays a role in the BBB disruption of the fatal BE of DKA. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：138 / 148

页数：11

共 51 条

[1] Astrocytes produce dendritic cell-attracting chemokines in vitro and in multiple sclerosis lesions [J].

Ambrosini, E ;

Remoli, ME ;

Giacomini, E ;

Rosicarelli, B ;

Serafini, B ;

Lande, R ;

Aloisi, F ;

Coccia, EM .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2005, 64 (08) :706-715

[2]

Ceriello A, 2001, DIABETOLOGIA, V44, P834

[3]

Ceriello Antonio, 2006, Endocr Pract, V12 Suppl 1, P60

[4] Diabetes-related changes in rat cerebral occludin and zonula occludens-1 (ZO-1) expression [J].

Chehade, JM ;

Haas, MJ ;

Mooradian, AD .

NEUROCHEMICAL RESEARCH, 2002, 27 (03) :249-252

[5] Modulation of the purinergic P2X7 receptor attenuates lipopolysaccharide-mediated microglial activation and neuronal damage in inflamed brain [J].

Choi, Hyun B. ;

Ryu, Jae K. ;

Kim, Seung U. ;

McLarnon, James G. .

JOURNAL OF NEUROSCIENCE, 2007, 27 (18) :4957-4968

[6]

Dalton RR, 2003, ANN CLIN LAB SCI, V33, P435

[7] CORRELATES OF BRAIN EDEMA IN UNCONTROLLED IDDM [J].

DURR, JA ;

HOFFMAN, WH ;

SKLAR, AH ;

ELGAMMAL, T ;

STEINHART, CM .

DIABETES, 1992, 41 (05) :627-632

[8] The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children [J].

Edge, J. A. ;

Jakes, R. W. ;

Roy, Y. ;

Hawkins, M. ;

Winter, D. ;

Ford-Adams, M. E. ;

Murphy, N. P. ;

Bergomi, A. ;

Widmer, B. ;

Dunger, D. B. .

DIABETOLOGIA, 2006, 49 (09) :2002-2009

[9] The risk and outcome of cerebral oedema developing during diabetic ketoacidosis [J].

Edge, JA ;

Hawkins, MM ;

Winter, DL ;

Dunger, DB .

ARCHIVES OF DISEASE IN CHILDHOOD, 2001, 85 (01) :16-20

[10] RELATION OF COLLOID OSMOTIC-PRESSURE TO ARTERIAL HYPOXEMIA AND CEREBRAL EDEMA DURING CRYSTALLOID VOLUME LOADING OF PATIENTS WITH DIABETIC-KETOACIDOSIS [J].

FEIN, IA ;

RACKOW, EC ;

SPRUNG, CL ;

GRODMAN, R .

ANNALS OF INTERNAL MEDICINE, 1982, 96 (05) :570-575

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