title: Poor outcome of experimental ischemic stroke in type 2 diabetic rats: impaired circulating endothelial progenitor cells mobilization.
abstract: BACKGROUND
  It is well accepted that type 2 diabetic mellitus (T2DM) results in the poor outcome of ischemic stroke. However, the mechanisms by which T2DM causes aggravated cerebral ischemic/reperfusion (I/R) injury are not clear. Recently, endothelial progenitor cells (EPCs) are considered to be related with the outcome of ischemic stroke. More importantly, T2DM can affect the function of circulating EPCs. This study tried to investigate whether T2DM worsens the cerebral I/R injury via affecting circulating EPCs.
  
  
  METHODS
  We used high-fat diet-fed and low-dose streptozotocin-treated male rats receiving middle cerebral artery occlusion surgery as animal model of focal cerebral I/R injury with T2DM (diabetic operated). And the rats were divided into 4 groups: normal sham, diabetic sham, normal operated, and diabetic operated. We measured the circulating EPCs counts and the levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in peripheral plasma of 4 groups.
  
  
  RESULTS
  We found that diabetic rats subjected to I/R exhibited significantly severe deterioration in neurologic deficits compared with nondiabetic counterparts, which manifested higher infarct volume and cell apoptosis as well as lower neurologic defective score. There was no significant difference on the plasma glucose of groups before cerebral I/R injury compared with that of the groups posterior to cerebral I/R injury despite cerebral I/R injury had the tendency to increase the plasma glucose no matter in the presence or the absence of T2DM. In addition, there were the marked downregulation of circulating EPCs counts and the levels of VEGF and eNOS in diabetic rats before the cerebral I/R injury. Despite I/R injury without T2DM, there was a significant increase in the circulating EPCs counts, the circulating EPCs counts in I/R injury with T2DM group were significantly decreased compared with those in the other 3 groups. We also observed that the level of eNOS was significantly improved by I/R injury without considering the presence of T2DM.
  
  
  CONCLUSIONS
  Thus, our present study suggested that it might be the impaired EPCs mobilization into the blood that contributed to the worse outcome of cerebral I/R injury with T2DM.
authors: Department of Critical-Care Medicine, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong Province.
authors: HongNa
authors: H
authors: Yang
authors: Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong Province.
authors: Shuang
authors: S
authors: Ma
authors: Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong Province.
authors: Ying
authors: Y
authors: Liu
authors: Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong Province.
authors: Yi
authors: Y
authors: Li
authors: Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong Province.
authors: Wei
authors: W
authors: Wu
authors: Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong Province.
authors: EnJi
authors: E
authors: Han
authors: Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong Province.
authors: GuoYong
authors: G
authors: Jia
authors: Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong Province; Brain Science Research Institute, Shandong University, Jinan, Shandong Province, China. Electronic address: qlyywcl@163.com.
authors: CuiLan
authors: C
authors: Wang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications; D002465:Cell Movement / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000473:pathology*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D008297:Male; D009460:Neurologic Examination; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications; D013311:Streptozocin / Q000633:toxicity; D020521:Stroke / Q000150:complications* / Q000209:etiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D013311:Streptozocin; D052250:Nitric Oxide Synthase Type III
keywords: Ischemic stroke; endothelial progenitor cells; mobilization; type 2 diabetes mellitus