Regional cerebral blood flow decreases during chronic and acute hyperglycemia.

Abstract

The presence of hyperglycemia prior to stroke or cardiac arrest can increase neuronal damage caused by brain ischemia. Acute hyperglycemia shows this effect in animal models of stroke. However, chronic hyperglycemia and chronic hyperglycemia with additional acute elevation of blood glucose are more common premorbid states for stroke patients. The effect of chronic hyperglycemia on regional cerebral blood flow (rCBF) is unclear but blood flow changes may play a role in this ischemic cell damage. We measured rCBF in awake restrained rats that had chronic hyperglycemia induced by treatment with streptozotocin. This was compared to that measured in rats made acutely hypergh/cemic by injecting glucose into the peritoneal space. rCBF was measured in 17 brain regions using [ u C]iodoantipyrine. During chronic hyperglycemia, when plasma glucose was 29 ^.m/ml, rCBF was decreased and a regional distribution of this effect was noted; 9 hindbrain regions showed a mean flow decrease of 14% while forebraln regions demonstrated less flow reduction. Acute elevation of plasma glucose during normoglycemia or superimposed on chronic hyperglycemia produced flow reductions of 7% for each 10 /xm/mJ increment in plasma glucose up to 60 /xm/ml. Both chronic and acute hyperglycemia are associated with decreased rCBF and the mechanism for this effect does not appear to adapt to chronic hyperglycemia. (Stroke 1987; 18:52-58) C LINICAL studies suggest that hyperglycemia is a risk factor for stroke 1 and that it increases brain injury during stroke or cardiac arrest.2 "4In animal models of stroke, acute hyperglycemia before ischemia increases mortality 3 and the number of neurons that die. 6 "* After transient ischemia, hyperglycemia increases and prolongs postischemic hyperemia 89 and enhances the heterogeneity of reperfusion. 10However, in normal animals an acute elevation of plasma glucose is associated with decreased regional cerebral blood flow (rCBF). 10 " This effect could limit compensatory blood flow mechanisms during an ischemic event.In clinical situations hyperglycemia, whether iatrogenic or the result of stroke itself, 12 is seldom as acute or as severe as that induced in animal models of stroke. Also, diabetics are frequently exposed to acute increases in blood glucose superimposed on a background of chronic hyperglycemia. Little is known about the effect of chronic hyperglycemia on rCBF. For these reasons we measured rCBF in awake restrained rats that had a moderate chronic hyperglycemia produced by treatment with streptozotocin. We found that chronic hyperglycemia was associated with decreased rCBF. Also, a specific regional distribution of this effect was noted with hindbrain regions manifesting CBF decreases during chronic hyperglycemia. Materials and Methods The isotope 4-iodo|7V-methyl-14 C]antipyrine, 53 mCi/mmol, was obtained from Amersham, Arlington Heights, El. Streptozotocin, 2-deoxy-2-([methylnitrosoamino]carbonyl)-amino(-<i-glucopyranose), was obtained from Sigma Chemical, St. Louis, Mo. Alloxan, 5,6-deoxyura...

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

“…For example, studies that assessed blood flow indirectly, by measuring erythrocyte velocity in cortical arterioles [40] or venous outflow [41] reported increases in cerebral blood flow. In contrast, studies that assessed blood flow at the tissue level, by measuring the cerebral uptake of tracers like [ 14 C]iodoantipyrine in awake or anaesthetized rats, consistently report flow reductions of 10 to 15 % during the first month of diabetes [12,13] and 10 to 30 % after 4 months of diabetes [42,14], with some degree of regional variation. Structural changes in the vasculature, including basement membrane thickening [15] could further impede energy delivery to the brain.…”

“…The functional deficits at these moderate levels of tissue hypoxia were suggested to be the consequence of oxygen-dependent changes in the metabolism of neurotransmitters rather than the effect of a failure in ATP and PCr production [37]. The threshold at which chronic reductions in cerebral blood flow lead to reductions in PCr and ATP is not exactly known but seems to exceed the 10±30 % flow reduction that can be expected to occur in the brain of STZ-diabetic rats [12,13,14,42]. In comparison, in peripheral nerves of diabetic rats, where blood flow is reduced by approximately 50 % [43,44], increased lactate and decreased PCr concentrations have been observed [22,45,46].…”

“…Cerebrovascular changes can be found in both diabetic rodents and patients. Studies in STZ-diabetic rats have shown regional reductions in cerebral blood flow within weeks [12,13] to months [14] after diabetes induction. Moreover, thickening of capillary basement membranes [15] and shortening of the length of the capillary network in the neocortex have been noted [8].…”

Region-Specific Cerebral Metabolic Alterations in Streptozotocin-Induced Type 1 Diabetic Rats: An in vivo Proton Magnetic Resonance Spectroscopy Study

“…28 It has been shown that the visual cortex of STZ-treated rats had normal cerebral blood flow and cerebral glucose metabolic rate (CMR glu ) between 3 and 4 weeks. 25,29 A electrophysiological study demonstrated normalization of visually evoked potential, after an earlier perturbation, in the occipital cortex of STZ-treated rats at 1 month. 30 The normalization of NAA metabolism in the visual cortex at 4 weeks perhaps reflect acclimation of neuronal function to elevated oxidative stress or impairment in glucose/energy metabolism imposed by sustained hyperglycemia.…”

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.…”