Perfusion Deficit Parallels Exacerbation of Cerebral Ischemia/Reperfusion Injury in Hyperglycemic Rats

Abstract

Magnetic resonance imaging (MRI) techniques were used to determine the effect of preexisting hyperglycemia on the extent of cerebral ischemia/reperfusion injury and the level of cerebral perfusion. Middle cerebral artery occlusion (MCAO) was induced by a suture insertion technique. Forty one rats were divided into hyperglycemic and normoglycemic groups with either 4 hours of continuous MCAO or 2 hours of MCAO followed by 2 hours of reperfusion. Diffusion-weighted imaging (DWI) was performed at 4 hours after MCAO to quantify the degree of injury in 6 brain regions. Relative cerebral blood flow (CBF) and cerebral blood volume (CBV) were estimated using gradient echo (GE) bolus tracking and steady-state spin echo (SE) imaging techniques, respectively. Brain injury correlated with the perfusion level measured in both SE CBV and dynamic GE CBF images. In the temporary MCAO model, mean lesion size in DWI was 118% larger and hemispheric CBV was reduced by 37% in hyperglycemic compared with normoglycemic rats. Hyperglycemia did not significantly exacerbate brain injury or CBV deficit in permanent MCAO models. We conclude that preexisting hyperglycemia increases acute postischemic MRI-measurable brain cellular injury in proportion to an associated increased microvascular ischemia.

Hyperglycemia in Acute Ischemic Stroke: A Vascular Perspective

“…Hyperglycemia was induced in rats by streptozotocin (STZ) 3 days before 2 h of tMCAO. After 2 h of reperfusion, penumbral CBF was reduced by 37% in hyperglycemic rats, matching an increase in acute ischemic territory as showed by diffusion imaging (Quast et al, 1997). Many of these animal studies also showed increased hemorrhage rates in hyperglycemic animals (Venables et al, 1985;Kawai et al, 1997), mimicking data from human studies.…”

“…Impaired NOmediated vasodilation has been shown in the cerebral circulation in diabetes and acute hyperglycemia (Schwaninger et al, 2003;Sercombe et al, 2004;Didion et al, 2005). Although there are studies consistent with eNOS uncoupling in the cerebral vasculature (Quast et al, 1997;Kinoshita et al, 1997), eNOS uncoupling has yet to be conclusively showed in this vascular bed. However, the rapidity of PPP inhibition and its potential effects on the cerebral vasculature are consistent with hyperglycemia's particularly detrimental role in acute ischemic stroke with reperfusion ( Figure 1B).…”

Hyperglycemia Accelerates Apparent Diffusion Coefficient-Defined Lesion Growth after Focal Cerebral Ischemia in Rats with and Without Features of Metabolic Syndrome

“…Single-slice magnetic resonance imaging studies indicate that the detrimental effects of high blood glucose occur early during lesion evolution after transient or permanent focal ischemia in the rat streptozotocin model of type 1 diabetes. 15,17 Subsequent developments in multislice diffusion-weighted imaging (DWI) mean that it is now possible to gain a comprehensive assessment of lesion expansion in the acute phase. In the present study, we have used this approach to investigate the effects of clinically relevant levels of hyperglycemia in rats with and without comorbidities associated with stroke, namely features of the 'metabolic syndrome'.…”

Stroke and diabetes: a dangerous liaison

“…17 This was associated with larger infarct size and is in agreement with previous work. [17][18][19][20] One study contradicts this hypothesis, possibly due to differences in hyperglycaemia severity. 21 Cerebral autoregulation is the process by which the blood supply to the brain is maintained despite changes in perfusion pressure.…”