Comparison of Neuroprotective Effect of Bevacizumab and Sildenafil following Induction of Stroke in a Mouse Model.
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 mm(3), mean penumbra area was 4.5 ± 2.03 mm(3), and hemispheric asymmetry was 106.5%. Corresponding values in the bevacizumab group (n = 19) were 17.79 ± 5.80 mm(3), 7.3 ± 3.5 mm(3), and 108.6%; in the delayed (6 h) bevacizumab injected mice (n = 7) they were 9.80 ± 8.00 mm(3), 2.4 ± 2.0 mm(3), and 98.2%; and in the sildenafil group (n = 16) they were 18.42 ± 5.41 mm(3), 5.7 ± 2.02 mm(3), 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.
Department of Neurosurgery, Rabin Medical Center-Beilinson Hospital, 49100 Petach Tikva, Israel.
Ivan
I
Novitzky
Department of Neurosurgery, Rabin Medical Center-Beilinson Hospital, 49100 Petach Tikva, Israel; Krieger Eye Research Laboratory, Felsenstein Medical Research Center, 49202 Petach Tikva, Israel.
Neelan J
NJ
Marianayagam
Krieger Eye Research Laboratory, Felsenstein Medical Research Center, 49202 Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv, Israel.
Shirel
S
Weiss
Pediatric Ophthalmology Unit, Schneider Children's Medical Center of Israel, 49100 Petach Tikva, Israel.
Orkun
O
Muhsinoglu
Krieger Eye Research Laboratory, Felsenstein Medical Research Center, 49202 Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv, Israel.
Moran
M
Fridman
Krieger Eye Research Laboratory, Felsenstein Medical Research Center, 49202 Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv, Israel.
Tamar Azrad
TA
Leibovitch
Krieger Eye Research Laboratory, Felsenstein Medical Research Center, 49202 Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv, Israel; Pediatric Ophthalmology Unit, Schneider Children's Medical Center of Israel, 49100 Petach Tikva, Israel.
Nitza
N
Goldenberg-Cohen
Department of Neurosurgery, Rabin Medical Center-Beilinson Hospital, 49100 Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv, Israel.
Shalom
S
Michowiz
D020533:Angiogenesis Inhibitors; D000818:Animals; D000068258:Bevacizumab / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D000068677:Sildenafil Citrate / Q000008:administration & dosage*; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage
D020533:Angiogenesis Inhibitors; D018696:Neuroprotective Agents; D014665:Vasodilator Agents; D000068258:Bevacizumab; D000068677:Sildenafil Citrate