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

Abstract

Poststroke hyperglycemia is associated with a poor outcome yet clinical management is inadequately informed. We sought to determine whether clinically relevant levels of hyperglycemia exert detrimental effects on the early evolution of focal ischemic brain damage, as determined by magnetic resonance imaging, in normal rats and in those modeling the 'metabolic syndrome'. Wistar Kyoto (WKY) or fructose-fed spontaneously hypertensive stroke-prone (ffSHRSP) rats were randomly allocated to groups for glucose or vehicle administration before permanent middle cerebral artery occlusion. Diffusion-weighted imaging was carried out over the first 4 hours after middle cerebral artery occlusion and lesion volume calculated from apparent diffusion coefficient maps. Infarct volume and immunostaining for markers of oxidative stress were measured in the fixed brain sections at 24 hours. Hyperglycemia rapidly exacerbated early ischemic damage in both WKY and ffSHRSP rats but increased infarct volume only in WKY rats. There was only limited evidence of oxidative stress in hyperglycemic animals. Acute hyperglycemia, at clinically relevant levels, exacerbates early ischemic damage in both normal and metabolic syndrome rats. Management of hyperglycemia may have greatest benefit when performed in the acute phase after stroke in the absence or presence of comorbidities.

Impact of stroke co-morbidities on cortical collateral flow following ischaemic stroke

“…This may explain, in part at least, our previous report of more rapid growth of ischaemic brain lesions, as determined by diffusion-weighted MRI, following pMCAO in acute hyperglycaemic rats compared to normoglycaemic controls. 23 It is also consistent with patient studies linking acute hyperglycaemia (defined as sustained blood glucose concentration above 6.0 mmol/L), with poorer functional outcome and higher mortality following stroke. 47,48,49,50,51,52,53,54 Further, a recent study 55 showed that hyperglycaemia in stroke patients with good collaterals decreases clinical prognosis and had no effect on patients with poor collateral recruitment.…”

An atypical role for the myeloid receptor Mincle in central nervous system injury

“…37 Throughout the brain, in both infarct and non-ischemic tissue, Mincle + cells were always associated with the vasculature. Monoclonal antibodies 4A9 (rat) and 16E3 (mouse) provided the same result (Figure 6).…”

“…37 Antibodies are described in the supplementary methods. Images were acquired using an Olympus BX61 microscope (Japan).…”

Association of Baseline Hyperglycemia With Outcomes of Patients With and Without Diabetes With Acute Ischemic Stroke Treated With Intravenous Thrombolysis: A Propensity Score–Matched Analysis From the SITS-ISTR Registry

“…Experimental models suggest that hyperglycaemia following ischaemia results in blood-brain barrier dysfunction through an increase in oxidative stress and matrix metalloproteinase-9 activity (29). Post-ischaemic hyperglycaemia has also been associated with exacerbation of ischaemic neuronal damage mediated by transporter signalling (30,31), in both normal animals and animals with metabolic syndrome (32), and with ineffective collateral circulation due to impaired cerebrovascular reactivity (33). Interestingly, in a small cohort increased blood glucose was associated with greater acute-subacute lactate production and reduced salvage of brain tissue only in AIS patients with perfusion-diffusion mismatch, and not in AIS patients without evidence of viable penumbra on neuroimaging (34).…”