Comparison of Neuroprotective Effect of Bevacizumab and Sildenafil following Induction of Stroke in a Mouse Model

• Published in: BioMed research international 2016-01, Vol.2016 (2016), p.1-8
• Main Authors: Michowiz, Shalom, Leibovitch, Tamar Azrad, Fridman, Moran, Muhsinoglu, Orkun, Weiss, Shirel, Marianayagam, Neelan J., Novitzky, Ivan, Goldenberg-Cohen, Nitza
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors; Animals; Bevacizumab - administration & dosage; Binding sites; Biosynthesis; Brain research; Carotid arteries; Comparative analysis; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Ischemia; Kidneys; Laboratories; Male; Medical research; Mice; Mice, Inbred C57BL; Neuroprotective Agents - administration & dosage; Oxidative stress; Proteins; Rodents; Sildenafil; Sildenafil Citrate - administration & dosage; Smooth muscle; Stroke; Stroke - diagnosis; Stroke - drug therapy; Stroke - pathology; Studies; Treatment Outcome; Tumors; Vascular endothelial growth factor; Vasodilator Agents - administration & dosage; Veins & arteries
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2016/3938523

To evaluate the effect of bevacizumab and sildenafil on stroke parameters in a mouse model, middle cerebral artery occlusion was induced in male C57Bl/6 mice using an intra-arterial filament method. The filament was removed after 60 minutes, and the mice were immediately given a single intraperitoneal injection of saline, bevacizumab, or sildenafil. An additional group of mice (n=7) received bevacizumab 6 h after MCAO induction. The mice were euthanized 24 hours later and evaluated for infarct area and brain edema using triphenyltetrazolium chloride staining and ImageJ. In the saline-treated mice (n=16), total stroke volume was 19.20±6.38 mm3, mean penumbra area was 4.5±2.03 mm3, and hemispheric asymmetry was 106.5%. Corresponding values in the bevacizumab group (n=19) were 17.79±5.80 mm3, 7.3±3.5 mm3, and 108.6%; in the delayed (6 h) bevacizumab injected mice (n=7) they were 9.80±8.00 mm3, 2.4±2.0 mm3, and 98.2%; and in the sildenafil group (n=16) they were 18.42±5.41 mm3, 5.7±2.02 mm3, and 109.9%. The bevacizumab group had a significantly larger mean penumbra area when given immediately and smaller total stroke area in both groups than the saline- (p=0.03) and sildenafil-treated (p=0.003) groups. Only delayed bevacizumab group had reduced edema. Bevacizumab, injected immediately or delayed after injury, exerts a neuroprotective/salvage effect, whereas immediate treatment with sildenafil does not. Inflammation may play a role in the neuroprotective effect.