title: Vascularization pattern after ischemic stroke is different in control versus diabetic rats: relevance to stroke recovery.
abstract: OBJECTIVE
  Pre-existing diabetes mellitus worsens brain functionality in ischemic stroke. We have previously shown that type 2 diabetic rats exhibit enhanced dysfunctional cerebral neovascularization and when these rats are subjected to cerebral ischemic reperfusion injury develop hemorrhagic transformation and greater neurological deficits. However, our knowledge of vascular and functional plasticity during the recovery phase of diabetic stroke is limited. This study tested the hypothesis that vascular repair is impaired in the poststroke period in diabetes mellitus, and this is associated with poor sensorimotor and cognitive function. We further hypothesized that glycemic control prevents impaired vascularization and improves functional outcome in diabetes mellitus.
  
  
  METHODS
  Vascularization was assessed in the ipsilateral and contralateral hemispheres in control, diabetes mellitus and diabetes mellitus plus metformin groups 14 days after ischemic reperfusion injury, as well as in respective sham controls. Three-dimensional reconstruction of the fluorescein isothiocyanate (FITC)-stained vasculature was achieved by confocal microscopy, and stereological parameters, including vascular volume and surface area, were measured. Astrogliosis was determined by glial fibrillary acidic protein staining. The relative rates of sensorimotor recovery, cognitive decline, and spontaneous activity were assessed.
  
  
  RESULTS
  Vascular density in the peri-infarct area was significantly reduced in diabetes mellitus, whereas there was reparative neovascularization in control rats. Astroglial swelling and reactivity were more pronounced in diabetic stroke compared with control stroke. Diabetes mellitus blunted sensorimotor recovery and also exacerbated anxiety-like symptoms and cognitive deficits. Glycemic control started after stroke partially prevented these changes.
  
  
  CONCLUSIONS
  Diabetes mellitus impairs poststroke reparative neovascularization and impedes the recovery. Glycemic control after stroke can improve neurovascular repair and improve functional outcome.
authors.affiliation: From the Department of Physiology, Charlie Norwood Veterans Administration Medical Center, Augusta, GA (R.P., W.L., S.C.F., A.E.); Program in Clinical and Experimental Therapeutics, University of Georgia College of Pharmacy, Augusta, GA (R.P., S.C.F., A.E.); and Departments of Physiology (W.L., Z.Q., A.E.), and Biostatistics (M.A.J.), Georgia Regents University, Augusta, GA.
authors.forename: Roshini
authors.initials: R
authors.lastname: Prakash
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.forename: Zhi
authors.initials: Z
authors.lastname: Qu
authors.forename: Maribeth A
authors.initials: MA
authors.lastname: Johnson
authors.forename: Susan C
authors.initials: SC
authors.lastname: Fagan
authors.forename: Adviye
authors.initials: A
authors.lastname: Ergul
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018919:Neovascularization, Physiologic; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D020521:Stroke / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
keywords: animal behavior; astrocytes; diabetes mellitus; metformin; neovascularization; recovery; type 2
references.citation: J Pharmacol Exp Ther. 2012 Aug;342(2):407-15
references.pmid: 22570365
references.citation: J Neurosci. 2012 Apr 11;32(15):5132-43
references.pmid: 22496559
references.citation: Clin Sci (Lond). 2006 Sep;111(3):171-83
references.pmid: 16901264
references.citation: Diabetes Metab Res Rev. 2006 Jul-Aug;22(4):323-30
references.pmid: 16444763
references.citation: Proc Natl Acad Sci U S A. 2011 May 17;108(20):8467-72
references.pmid: 21536893
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R952-9
references.pmid: 19176890
references.citation: Diabetes Care. 1997 Sep;20(9):1388-95
references.pmid: 9283785
references.citation: Stroke. 2007 Feb;38(2):431-40
references.pmid: 17234988
references.citation: Brain Res. 2003 May 16;972(1-2):31-7
references.pmid: 12711075
references.citation: J Cereb Blood Flow Metab. 2011 Apr;31(4):1119-32
references.pmid: 21081957
references.citation: Diabetes. 1999 May;48(5):937-42
references.pmid: 10331395
references.citation: J Neurol Sci. 2008 Feb 15;265(1-2):97-101
references.pmid: 17610903
references.citation: Wien Med Wochenschr. 2010 Jan;160(1-2):8-19
references.pmid: 20229156
references.citation: Curr Opin Neurobiol. 2007 Feb;17(1):120-7
references.pmid: 17223033
references.citation: Diabetes Metab Res Rev. 2004 Jul-Aug;20(4):268-87
references.pmid: 15250030
references.citation: Biomed Pharmacother. 2010 Mar;64(3):208-13
references.pmid: 19932587
references.citation: Pol Arch Med Wewn. 2008 Nov;118(11):619-21
references.pmid: 19140564
references.citation: Neurobiol Aging. 2005 Dec;26 Suppl 1:11-6
references.pmid: 16223549
references.citation: Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1603-9
references.pmid: 15920034
references.citation: Curr Opin Investig Drugs. 2010 Mar;11(3):298-308
references.pmid: 20178043
references.citation: Lancet Neurol. 2011 Nov;10(11):969-77
references.pmid: 21958949
references.citation: FEBS J. 2009 Sep;276(17):4644-52
references.pmid: 19664070
references.citation: Am J Epidemiol. 2008 Nov 15;168(10):1132-9
references.pmid: 18836152
references.citation: Circulation. 2011 Jul 19;124(3):314-23
references.pmid: 21730306
references.citation: Clin Sci (Lond). 2008 Feb;114(3):251-6
references.pmid: 17922677
references.citation: Stroke. 1994 Oct;25(10):1977-84
references.pmid: 8091441
references.citation: Lancet. 1998 Sep 12;352(9131):854-65
references.pmid: 9742977
references.citation: Rom J Morphol Embryol. 2010;51(4):725-31
references.pmid: 21103633
references.citation: Muscle Nerve. 2001 Aug;24(8):1000-19
references.pmid: 11439375
references.citation: World Neurosurg. 2011 Dec;76(6 Suppl):S85-90
references.pmid: 22182277
references.citation: Stroke. 2012 Aug;43(8):2270-4
references.pmid: 22618382
references.citation: Vascul Pharmacol. 2009 Jul;51(1):44-9
references.pmid: 19258053
references.citation: Stroke. 1994 Sep;25(9):1794-8
references.pmid: 7521076
references.citation: J Cereb Blood Flow Metab. 2010 Dec;30(12):1928-38
references.pmid: 20664613
references.citation: Stroke. 2002 Dec;33(12):2985-91
references.pmid: 12468801
references.citation: Diabetes. 2010 Jan;59(1):228-35
references.pmid: 19808897
references.citation: Eur J Endocrinol. 2008 May;158(5):631-41
references.pmid: 18426821
references.citation: J Cereb Blood Flow Metab. 2008 Oct;28(10):1652-5
references.pmid: 18575459
references.citation: Neurology. 2012 Jan 24;78(4):279-85
references.pmid: 22238419
references.citation: Neuroepidemiology. 2011;37(1):21-30
references.pmid: 21757961
references.citation: Curr Atheroscler Rep. 2001 Sep;3(5):383-91
references.pmid: 11487449
references.citation: Curr Cardiol Rev. 2010 Aug;6(3):238-44
references.pmid: 21804783
references.citation: BMJ. 2000 Aug 12;321(7258):405-12
references.pmid: 10938048
references.citation: Stroke. 2008 Oct;39(10):2712-9
references.pmid: 18635849
references.citation: Dement Geriatr Cogn Disord. 2011;31(4):291-9
references.pmid: 21502760
references.citation: Diabetes. 2012 Jun;61(6):1533-42
references.pmid: 22403298
references.citation: Stroke. 2007 Feb;38(2 Suppl):827-31
references.pmid: 17261747
references.citation: Lancet Neurol. 2009 May;8(5):491-500
references.pmid: 19375666
references.citation: Stroke. 2003 Mar;34(3):688-94
references.pmid: 12624292
references.citation: J Neurosci. 2005 Nov 2;25(44):10167-79
references.pmid: 16267224
references.citation: J Cereb Blood Flow Metab. 2001 Jan;21(1):52-60
references.pmid: 11149668
references.citation: J Diabetes Complications. 2009 Jul-Aug;23(4):249-54
references.pmid: 18417372