Abstract
BackgroundInterruption of flow through of cerebral blood vessels results in acute ischemic stroke. Subsequent breakdown of the blood brain barrier increases cerebral injury by the development of vasogenic edema and secondary hemorrhage known as hemorrhagic transformation (HT). Diabetes is a risk factor for stroke as well as poor outcome of stroke. The current study tested the hypothesis that diabetes-induced changes in the cerebral vasculature increase the risk of HT and augment ischemic injury.MethodsDiabetic Goto-Kakizaki (GK) or control rats underwent 3 hours of middle cerebral artery occlusion and 21 h reperfusion followed by evaluation of infarct size, hemorrhage and neurological outcome.ResultsInfarct size was significantly smaller in GK rats (10 ± 2 vs 30 ± 4%, p < 0.001). There was significantly more frequent hematoma formation in the ischemic hemisphere in GK rats as opposed to controls. Cerebrovascular tortuosity index was increased in the GK model (1.13 ± 0.01 vs 1.34 ± 0.06, P < 0.001) indicative of changes in vessel architecture.ConclusionThese findings provide evidence that there is cerebrovascular remodeling in diabetes. While diabetes-induced remodeling appears to prevent infarct expansion, these changes in blood vessels increase the risk for HT possibly exacerbating neurovascular damage due to cerebral ischemia/reperfusion in diabetes.
Highlights
Interruption of flow through of cerebral blood vessels results in acute ischemic stroke
Slides were viewed using a Zeiss Axiovert microscope (Carl Zeiss, Inc., Thornwood, NY) and media:lumen ratios (M/L) were analyzed using Spot software (Diagnostic Instruments, MI). 4 measurements were made per section and each animal had at least 3 sections as we reported previously [9]
IFnifgaurcrtesi1ze is reduced in diabetes Infarct size is reduced in diabetes. (A) A representative image showing TTC staining for infarct size and localization in control Wistar (n = 10) and diabetic GK rats (n = 9). (B) Bar graph depicting infarct size in all the animals
Summary
Interruption of flow through of cerebral blood vessels results in acute ischemic stroke. Diabetes is a risk factor for stroke as well as poor outcome of stroke. The current study tested the hypothesis that diabetes-induced changes in the cerebral vasculature increase the risk of HT and augment ischemic injury. Ischemic stroke is a leading cause of death and disability in the United States and diabetes is the most rapidly increasing risk factor for stroke. Is the incidence of stroke increased among diabetics, but stroke patients with diabetes have a worse outcome. Mortality is increased in diabetics at one week, one month and three months after stroke, and diabetic stroke survivors have more profound neurologic deficits and disability [2]. A recent study reported that persistent post-stroke hyperglycemia causes infarct expansion and worse clinical outcome [4]. Vascular complications of diabetes characterized by vascular dysfunction and pathological remodeling contribute to increased cardiovascular mortality and morbidity in diabetes, yet, changes in the cerebrovascular structure remain unknown
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