title: Diabetes Worsens Ischemia-Reperfusion Brain Injury in Rats Through GSK-3β.
abstract: BACKGROUND
  Diabetes aggravates brain injury after cerebral ischemia/reperfusion (I/R).
  
  
  OBJECTIVE
  To investigate whether limb I/R causes cerebral injury in a rat diabetes model and whether glycogen synthase kinase-3β (GSK-3β) is involved.
  
  
  METHODS
  Male adult Sprague-Dawley rats were assigned into streptozotocin-induced diabetes (n = 30; blood glucose ≥16.7 mmol/L) or control (n = 20) groups, further subdivided into diabetes I/R (3-hour femoral artery/vein clamping), diabetes-I/R + TDZD-8 (I/R plus GSK-3β inhibitor), diabetes-sham, control-sham and control-I/R groups (n = 10 each). Cortical and hippocampal morphology (hematoxylin/eosin); hippocampal CA1 apoptosis (TUNEL assay); cleaved caspase-3 (apoptosis), and Iba1 (microglial activation) protein expression (immunohistochemistry); phosphorylated/total GSK-3β and nuclear factor-κB (NF-κB) protein levels (Western blotting); and serum and brain tissue tumor necrosis factor (TNF)-α levels (enzyme-linked immunosorbent assay) were analyzed.
  
  
  RESULTS
  The diabetes-I/R group showed greater cortical and hippocampal injury, apoptosis, cleaved caspase-3 expression and Iba1 expression than the control-I/R group; TDZD-8 reduced injury/apoptosis and cleaved caspase-3/Iba1 expressions. The diabetes-I/R group had lower p-GSK-3β and p-NF-κBp65 expression than the control-I/R group (P < 0.05); TDZD-8 increased p-GSK-3β expression but decreased p-NF-κBp65 expression (P < 0.05). The diabetes-I/R group showed higher elevation of serum and brain tissue TNF-α than the control-I/R group (P < 0.05); TDZD-8 reduced TNF-α production.
  
  
  CONCLUSIONS
  Diabetes exacerbates limb I/R-induced cerebral damage and activates NF-κB and GSK-3β.
authors.affiliation: Department of Anaesthesiology, Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Ou
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xiao
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Zhu
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D003925:Diabetic Angiopathies / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D005121:Extremities / Q000098:blood supply; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D013830:Thiadiazoles / Q000494:pharmacology
chemical_list: C494356:4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione; D016328:NF-kappa B; D013830:Thiadiazoles; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3