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Cerebrovascular effects of glibenclamide investigated using high-resolution magnetic resonance imaging in healthy volunteers.

ABSTRACT: Glibenclamide inhibits sulfonylurea receptor (SUR), which regulates several ion channels including SUR1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel and ATP-sensitive potassium (K_ATP) channel. Stroke upregulates SURl-TRPM4 channel, which causes a rapid edema formation and brain swelling. Glibenclamide may antagonize the formation of cerebral edema during stroke. Preclinical studies showed that glibenclamide inhibits K_ATP channel-induced vasodilation without altering the basal vascular tone. The in vivo human cerebrovascular effects of glibenclamide have not previously been investigated.In a randomized, double-blind, placebo-controlled, three-way cross-over study, we used advanced 3 T MRI methods to investigate the effects of glibenclamide and K_ATP channel opener levcromakalim on mean global cerebral blood flow (CBF) and intra- and extracranial artery circumferences in 15 healthy volunteers. Glibenclamide administration did not alter the mean global CBF and the basal vascular tone. Following levcromakalim infusion, we observed a 14% increase of the mean global CBF and an 8% increase of middle cerebral artery (MCA) circumference, and glibenclamide did not attenuate levcromakalim-induced vascular changes. Collectively, the findings demonstrate the vital role of K_ATP channels in cerebrovascular hemodynamic and indicate that glibenclamide does not inhibit the protective effects of K_ATP channel activation during hypoxia and ischemia-induced brain injury.

SUBMITTER: Al-Karagholi MA

PROVIDER: S-EPMC8142144 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:INTRODUCTION:The menisci are responsible for several functions. They are shock absorbers during dynamic loading on the knee and provide a broader surface area on which to distribute stress evenly to the tibia and femur. These functions allow for smoother movement and greater stability of the knee joint. Meniscal injury can be a great impediment to the function of the knee. Therefore, in the case of meniscal injury, our main concern is the relief of patient symptoms, followed by consequent restoration of meniscal function to the greatest of our ability. To prevent the long terms effects of a meniscectomy, meniscal allograft transplantation (MAT) was developed. The potential of using the size of the contralateral healthy menisci, to determine the size of the menisci to be replaced, will be discussed. METHODS:Knee MRIs done on healthy patients in the past 5 years were reviewed. Magnetic Resonance Imaging was performed using a 3-T scanner. Each individual was examined with knee joints in full extension. Measurements were performed two separate times, two weeks apart. A mean of three measurements was made during each session to reduce error. Thirty-eight normal bilateral knee joints MRIs remained (16 males, 22 females). Participants were sampled from the institutional Picture Archiving and Communication System (PACS). Age, gender, and the medial meniscal and lateral meniscal size of both knees were recorded. The laterality of the menisci was compared between both knees in each patient. RESULTS:A total of 38 patients were included in this study, with a mean age of 37.39 (±9.50) years. They were 16 (42.1%) men and 22 (57.9%) women. We didn't find any significant difference in the mid-coronal section between left and right knees meniscal measurements. None of the measurements were significantly different between men and women. There was no significant difference in the medial mid-sagittal section or lateral mid-sagittal section between left and right knee meniscal measurements. CONCLUSION:The results obtained in this study may support the use of MRI of the bilateral knee to obtain an appropriately sized allograft.

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Cerebrovascular effects of glibenclamide investigated using high-resolution magnetic resonance imaging in healthy volunteers.

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