Background and purpose
Energy depletion is a critical factor leading to cell death and brain dysfunction after ischemic stroke. In this study we investigated whether energy depletion is involved in hyperglycemia-induced hemorrhagic transformation (HT) after ischemic stroke and determined the pathway underlying the beneficial effects of hyperbaric oxygen (HBO).
Methods
After 2 hours MCAO, hyperglycemia was induced by injecting of 50% dextrose (6 ml/kg) intraperitoneally at the onset of reperfusion. Immediately after it rats were exposed to HBO at 2 atmospheres absolutes (ATA) for 1 hour. ATP synthase inhibitor Oligomycin A (Olig A), NAMPT inhibitor FK866 or Sirt1 siRNA was administrated for interventions. Infarct volume, hemorrhagic volume, neurobehavioral deficits were recorded; the level of blood glucose, ATP and NAD+ and the activity of NAMPT were monitored; the expression of Sirt1, acetylated P53, acetylated NF-κB and cleaved caspase 3 were detected by western blots; the activity of MMP-9 was assayed by zymography.
Results
Hyperglycemia deteriorated energy metabolism and reduced the level of ATP and NAD+, exaggerated hemorrhagic transformation, blood-brain barrier disruption and neurological deficits after MCAO. HBO treatment increased the levels of the ATP and NAD+ and consequently increased Sirt1, resulting in attenuation of hemorrhagic transformation, brain infarction as well as improvement of neurological function in hyperglycemic MCAO rats.
Conclusion
HBO induced activation of ATP/NAD+/Sirt1 pathway and protected blood-brain barrier in hyperglycemic MCAO rats. HBO might be promising approach for treatment of acute ischemic stroke patients, especially patients with diabetes or treated with rtPA.
Intracranial atherosclerotic disease is increasingly recognized as a major stroke subtype worldwide. Current diagnostic evaluation of atherosclerotic disease of the middle cerebral artery (MCA) relies on detection of stenoses with luminographic imaging studies that do not directly visualize plaque unlike high-resolution MRI. This retrospective study seeks to evaluate the accuracy of high-resolution MRI vessel wall imaging, computed tomographic angiography (CTA) and digital subtraction angiography (DSA) in measuring the degree of stenosis within the MCA. 28 recently symptomatic patients with MCA territory symptoms underwent preliminary imaging with CTA followed by high-resolution MRI at 3-Tesla and definitive imaging with DSA for detection of M1 territory steno-occlusive lesions. Measurements of MCA segments on MRI and CTA were compared with reference to DSA values. Sensitivity and specificity of high-resolution MRI vessel wall imaging, CTA using maximum intensity projection (MIP) and CTA using volume rendering (VR) for the detection of stenosis > 50 % and occlusion were 80.0 and 53.6 %, 72.2 and 72.7 %, and 77.8 and 18.2 %, respectively. MRI-derived values correlated better with DSA (Spearman R = 0.68, p < 0.01) than CTA MIP and VR (Spearman R = 0.45, 0.22; p = 0.02, 0.24, respectively). High-resolution MRI of the MCA is capable of accurately measuring the degree of stenosis and is more sensitive than CTA in a sample of high-risk, symptomatic patients. This study, combined with previous reports, supports the potential of morphological MRI to measure intracranial atherosclerotic plaque non-invasively.
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