Beta adrenoceptor blockade ameliorates impaired glucose tolerance and alterations of the cerebral ceramide metabolism in an experimental model of ischemic stroke

Therapeutic Advances in Neurological Disorders
Sebastian LugerWaltraud Pfeilschifter

Abstract

Sphingolipids are versatile signaling molecules derived from membrane lipids of eukaryotic cells. Ceramides regulate cellular processes such as proliferation, differentiation and apoptosis and are involved in cellular stress responses. Experimental evidence suggests a pivotal role of sphingolipids in the pathogenesis of cardiovascular diseases, including ischemic stroke. A neuroprotective effect has been shown for beta-adrenergic antagonists in rodent stroke models and supported by observational clinical data. However, the exact underlying pathophysiological mechanisms are still under investigation. We aimed to examine the influence of propranolol on the ceramide metabolism in the stroke-affected brain. Mice were subjected to 60 or 180 min transient middle cerebral artery occlusion (tMCAO) and infarct size, functional neurological deficits, glucose tolerance, and brain ceramide levels were assessed after 12, 24, and 72 h to evaluate whether the latter two processes occur in a similar time frame. Next, we assessed the effects of propranolol (10 mg/kg bw) at 0, 4 and 8 h after tMCAO and FTY720 (fingolimod; 1 mg/kg) on infarct size, functional outcome, immune cell counts and brain ceramide levels at 24 h after 60 min tMCAO. We fou...Continue Reading

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Citations

Mar 30, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Lv HongZhang Guojun
Jul 3, 2021·International Journal of Molecular Sciences·Rezan Ashayeri AhmadabadMaryam Khaleghi Ghadiri
Jul 18, 2021·Frontiers in Neuroendocrinology·Pan CuiJunwei Hao

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Methods Mentioned

BETA
FACS
biosensor

Software Mentioned

ARRIVE
ImageJ
GraphPad
Prism

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