PMID- 24886035
OWN - NLM
STAT- MEDLINE
DCOM- 20141201
LR  - 20220309
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 11
DP  - 2014 May 1
TI  - Deregulation of inflammatory response in the diabetic condition is associated 
      with increased ischemic brain injury.
PG  - 83
LID - 10.1186/1742-2094-11-83 [doi]
AB  - BACKGROUND: Although elicited inflammation contributes to tissue injury, a 
      certain level of inflammation is necessary for subsequent tissue 
      repair/remodeling. Diabetes, a chronic low-grade inflammatory state, is a 
      predisposing risk factor for stroke. The condition is associated with delayed 
      wound healing, presumably due to disrupted inflammatory responses. With inclusion 
      of the diabetic condition in an experimental animal model of stroke, this study 
      investigates whether the condition alters inflammatory response and influences 
      stroke-induced brain injury. METHODS: C57BL/6 mice were fed a diabetic diet (DD) 
      for 8 weeks to induce an experimental diabetic condition or a normal diet (ND) 
      for the same duration. Gene expression of inflammatory factors including monocyte 
      chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), CCR2, and CD36 was 
      assessed in the peripheral immune cells and brains of normal and diabetic mice 
      before and after focal cerebral ischemia. The expression of these factors was 
      also determined in lipopolysaccharide (LPS)-treated cultured normal and diabetic 
      macrophages. Ischemic outcome was assessed in these mice at 3 days post-ischemia. 
      RESULTS: DD intervention in mice resulted in obesity and elevated insulin and 
      glucose level in the blood. The peritoneal immune cells from the diabetic mice 
      showed higher MCP-1 mRNA levels before and after stroke. Compared to normal mice, 
      diabetic mice showed reduced MCP-1, IL-6, and CCR2 gene expression in the brain 
      at 6 h post-ischemia. LPS-stimulated inflammatory responses were also reduced in 
      the diabetic macrophages. The diabetic mice showed larger infarct size and 
      percent swelling. CONCLUSIONS: These results showed that diabetic conditions 
      deregulate acute inflammatory response and that the condition is associated with 
      increased stroke-induced injury. The study suggests that interventions aimed at 
      restoring appropriate inflammatory response in peripheral immune 
      cells/macrophages may be beneficial in reducing stroke-induced brain injury in 
      subjects with chronic inflammatory conditions.
FAU - Kim, Eunhee
AU  - Kim E
FAU - Tolhurst, Aaron T
AU  - Tolhurst AT
FAU - Cho, Sunghee
AU  - Cho S
AD  - Burke-Cornell Medical Research Institute, White Plains, NY 10605, USA. 
      suc2002@med.cornell.edu.
LA  - eng
GR  - R01 HL082511/HL/NHLBI NIH HHS/United States
GR  - R01 NS077897/NS/NINDS NIH HHS/United States
GR  - NS07789/NS/NINDS NIH HHS/United States
GR  - HL082511/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140501
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Blood Glucose)
RN  - 0 (CD36 Antigens)
RN  - 0 (Cytokines)
RN  - 0 (Insulin)
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Brain Injuries/*complications/etiology
MH  - Brain Ischemia/complications
MH  - CD36 Antigens
MH  - Cells, Cultured
MH  - Cytokines/blood/genetics/*metabolism
MH  - Diabetes Mellitus, Experimental/*complications/etiology/pathology
MH  - Diet, Diabetic/adverse effects
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/*physiology
MH  - Insulin/blood
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Peritoneal Cavity/pathology
PMC - PMC4017808
EDAT- 2014/06/03 06:00
MHDA- 2014/12/15 06:00
PMCR- 2014/05/01
CRDT- 2014/06/03 06:00
PHST- 2014/02/04 00:00 [received]
PHST- 2014/03/26 00:00 [accepted]
PHST- 2014/06/03 06:00 [entrez]
PHST- 2014/06/03 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - 1742-2094-11-83 [pii]
AID - 10.1186/1742-2094-11-83 [doi]
PST - epublish
SO  - J Neuroinflammation. 2014 May 1;11:83. doi: 10.1186/1742-2094-11-83.