Crotalus atrox disintegrin reduces hemorrhagic transformation by attenuating matrix metalloproteinase-9 activity after middle cerebral artery occlusion in hyperglycemic male rats.

Autor: McBride DW; The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas.; Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, California., Gren ECK; Department of Earth and Biological Sciences, Loma Linda University School of Medicine, Loma Linda, California., Kelln W; Department of Earth and Biological Sciences, Loma Linda University School of Medicine, Loma Linda, California., Hayes WK; Department of Earth and Biological Sciences, Loma Linda University School of Medicine, Loma Linda, California., Zhang JH; Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, California.; Department of Neurosurgery, Loma Linda University School of Medicine, Loma Linda, California.; Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California.
Jazyk: angličtina
Zdroj: Journal of neuroscience research [J Neurosci Res] 2020 Jan; Vol. 98 (1), pp. 191-200. Date of Electronic Publication: 2018 Sep 22.
DOI: 10.1002/jnr.24334
Abstrakt: Hemorrhagic transformation after ischemic stroke is an independent predictor for poor outcome and is characterized by blood vessel rupture leading to brain edema. To date, no therapies for preventing hemorrhagic transformation exist. Disintegrins from the venom of Crotalus atrox have targets within the coagulation cascade, including receptors on platelets. We hypothesized that disintegrins from C. atrox venom can attenuate hemorrhagic transformation by preventing activation of matrix metalloproteinase after middle cerebral artery occlusion (MCAO) in hyperglycemic rats. We subjected 48 male Sprague-Dawley rats weighing 240-260 g to MCAO and hyperglycemia to induce hemorrhagic transformation of the infarction. At reperfusion, we administered either saline (vehicle), whole C. atrox venom (two doses were used), or fractionated C. atrox venom (HPLC Fraction 2). Rats were euthanized 24 hr post-ictus for measurement of infarction and hemoglobin volume. Reversed-phase HPLC was performed to fractionate the whole venom and peaks were combined to form Fraction 2, which contained the disintegrin Crotatroxin. Fraction 2 protected against hemorrhagic transformation after MCAO, and attenuated activation of matrix metalloproteinase-9. Administering matrix metalloproteinase antagonists prevented the protection by Fraction 2. The results of this study indicate that disintegrins found in C. atrox venom may have therapeutic potential for reducing hemorrhagic transformation after ischemic stroke. Moreover, the RP-HPLC fractions retained sufficient protein activity to suggest that gentler and less efficient orthogonal chromatographic methods may be unnecessary to isolate proteins and explore their function.
(© 2018 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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