title: Comparative analysis of the neurovascular injury and functional outcomes in experimental stroke models in diabetic Goto-Kakizaki rats.
abstract: Diabetes worsens functional outcome and is associated with greater hemorrhagic transformation (HT) after ischemic stroke. We have shown that diabetic Goto-Kakizaki (GK) rats develop greater HT and neurological deficit despite smaller infarcts after transient middle cerebral artery occlusion (MCAO) with the suture model. However, the impact of (1) the duration of ischemia/reperfusion (I/R); (2) the method of ischemia; and (3) acute glycemic control on neurovascular injury and functional outcome in diabetic stroke remained unanswered. Wistar and GK rats were subjected to variable MCAO by suture or embolus occlusion. A group of GK rats were treated with insulin or metformin before stroke with suture occlusion. In all groups, infarct size, edema, HT occurrence and severity, and functional outcome were measured. Infarct size at 24h was smaller in GK rats with both suture and embolic MCAO, but expanded with longer reperfusion period. Edema and HT were increased in GK rats after 90min and 3h occlusion with the suture model, but not in the embolic MCAO. Neurological deficit was greater in diabetic rats. These findings suggest that diabetes accelerates the development of HT and amplifies vascular damage in the suture model where blood flow is rapidly reestablished. Acute metformin treatment worsened the infarct size, HT, and behavior outcome, whereas insulin treatment showed a protective effect. These results suggest that the impact of ischemia/reperfusion on neurovascular injury and functional outcome especially in disease models needs to be fully characterized using different models of stroke to model the human condition.
authors.affiliation: Charlie Norwood Veterans Affairs Medical Center, Augusta, GA 30904, USA; Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.forename: Zhi
authors.initials: Z
authors.lastname: Qu
authors.forename: Roshini
authors.initials: R
authors.lastname: Prakash
authors.forename: Connie
authors.initials: C
authors.lastname: Chung
authors.forename: Handong
authors.initials: H
authors.lastname: Ma
authors.forename: Md Nasrul
authors.initials: MN
authors.lastname: Hoda
authors.forename: Susan C
authors.initials: SC
authors.lastname: Fagan
authors.forename: Adviye
authors.initials: A
authors.lastname: Ergul
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D020300:Intracranial Hemorrhages / Q000209:etiology / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology*; D020521:Stroke / Q000150:complications* / Q000473:pathology*
keywords: 2,3,5-triphenyltetrazolium chloride; AMP; AMP-activated protein kinase; AMPK; ANOVA; Adenosine monophosphate; Analysis of variance; BBB; Blood-brain barrier; Diabetes; ECA; Edema; External carotid artery; GK; Goto-Kakizaki; HT; Hemorrhagic transformation; I/R; Infarct; Ischemia/reperfusion; Ischemic stroke; MCAO; Metformin; Middle cerebral artery occlusion; NBG; Normal blood glucose; PE; Polyethylene; SEM; STAIR; Standard error of the mean; Stroke Therapy Academia Industry Roundtable committee; TTC; Tissue plasminogen activator; met; tPA