Crotalus atrox disintegrin reduces hemorrhagic transformation by attenuating matrix metalloproteinase-9 activity after middle cerebral artery occlusion in hyperglycemic male rats
| Autor: | Devin W. McBride, John H. Zhang, Eric C.K. Gren, William K. Hayes, Wayne Kelln |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Disintegrins Infarction Venom Pharmacology Matrix metalloproteinase Article Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Disintegrin Medicine Animals Platelet Receptor Crotalus atrox biology business.industry Infarction Middle Cerebral Artery biology.organism_classification medicine.disease Rats Disease Models Animal 030104 developmental biology Matrix Metalloproteinase 9 Hyperglycemia biology.protein Hemoglobin business Intracranial Hemorrhages 030217 neurology & neurosurgery Platelet Aggregation Inhibitors |
| Zdroj: | J Neurosci Res |
| ISSN: | 1097-4547 |
| Popis: | 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 Crotalus atrox venom can attenuate hemorrhagic transformation by preventing activation of matrix metalloproteinase after middle cerebral artery occlusion in hyperglycemic rats. We subjected 48 male Sprague-Dawley rats weighing 240–260 g to middle cerebral artery occlusion and hyperglycemia to induce hemorrhagic transformation of the infarction. At reperfusion, we administered either saline (vehicle), whole Crotalus atrox venom (two different doses were used), or fractionated Crotalus atrox venom (HPLC Fraction 2) to animals at reperfusion. Rats were euthanized 24 hours 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 middle cerebral artery occlusion, 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 Crotalus 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. |
| Databáze: | OpenAIRE |
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