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Magnesium sulfate protects blood–brain barrier integrity and reduces brain edema after acute ischemic stroke in rats

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Abstract

Brain edema is a fatal complication of acute ischemic stroke and associated with worse outcomes in patients. This study was designed to evaluate the effects of magnesium sulfate on vasogenic brain edema formation and blood–brain barrier (BBB) disruption caused by ischemia-reperfusion (IR) in a rat model of ischemic stroke. A total of 72 male Sprague-Dawley rats were categorized into the following three primary groups: sham, control ischemic, magnesium-sulfate-treated (300 mg/kg loading dose, followed by an additional 100 mg/kg) ischemic (n = 24 in each group). Transient focal cerebral ischemia was induced by 60-min-long occlusion of the left middle cerebral artery, followed by 24-h-long reperfusion. Sensorimotor deficits, infarct volume, and brain edema were evaluated at the end of the reperfusion period. The BBB permeability was assessed by Evans Blue extravasation technique. Lipid peroxidation levels were assessed by measuring the malondialdehyde content in the brain tissue homogenate, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase were detected according to the technical manual of the assay kits. Induction of cerebral ischemia in the control group produced considerable BBB damage in conjunction with severe brain edema formation. Treatment with magnesium sulfate significantly attenuated brain edema and protected BBB integrity in the ischemic lesioned hemisphere. In addition, magnesium sulfate reduced lipid peroxidation and increased antioxidant protection of brain tissue by upregulating the activities of antioxidant enzymes. Treatment with magnesium sulfate protected BBB integrity against IR-induced damage and reduced vasogenic edema formation partly via antioxidant mechanisms in a rat model of acute ischemic stroke.

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Acknowledgements

This research project was financially supported by Vice Chancellor for Research of the Ardabil University of Medical Sciences, Ardabil, Iran (grant No. 9607).

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Authors and Affiliations

  1. Department of Physiology, Medical School, Ardabil University of Medical Sciences, Ardabil, 56197, Iran

    Javad Shadman, Nooshin Sadeghian, Alireza Moradi & Hamdollah Panahpour

  2. Physiological Studies Research Center, Medical School, Ardabil University of Medical Sciences, Ardabil, Iran

    Javad Shadman, Nooshin Sadeghian, Alireza Moradi & Hamdollah Panahpour

  3. Department of Pharmacology, Pharmacy School, Ardabil University of Medical Sciences, Ardabil, Iran

    Shahab Bohlooli

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  1. Javad Shadman
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  2. Nooshin Sadeghian
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  5. Hamdollah Panahpour
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Correspondence to Hamdollah Panahpour.

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Shadman, J., Sadeghian, N., Moradi, A. et al. Magnesium sulfate protects blood–brain barrier integrity and reduces brain edema after acute ischemic stroke in rats. Metab Brain Dis 34, 1221–1229 (2019). https://doi.org/10.1007/s11011-019-00419-y

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