Effects of anti-VEGF antibody on blood–brain barrier disruption in focal cerebral ischemia

Orosomucoid1: Involved in vascular endothelial growth factor-induced blood–brain barrier leakage after ischemic stroke in mouse

“…Zhang et al (2000) first reported the dual roles of VEGF in the enhancement of cerebral microvascular perfusion and increase in the BBB leakage in the ischemic brain. This paradoxical role of VEGF in ischemic stroke was verified by several other studies (Chi et al, 2007;Kimura et al, 2005;Koyama et al, 2010;Li et al, 2008;Valable et al, 2005;Zhang et al, 2000). Consistent with these findings, our study also found that VEGF increased BBB disruption and brain edema, as evidenced by Evans blue extravasation and the brain water content measurements, respectively.…”

“…However, accumulating evidence from both basic and preclinical trials demonstrated that the risk-to-benefit ratio of the application of VEGF for ischemic stroke was high (Li et al, 2008;Manoonkitiwongsa, 2011). This finding may likely be due to the severe side effects of VEGF treatment, such as blood-brain barrier (BBB) disruption, brain edema and hemorrhagic transformation (Chi et al, 2007;Kanazawa et al, 2011;Kimura et al, 2005;Koyama et al, 2010;Li et al, 2008;Valable et al, 2005;Zhang et al, 2000). BBB, a vital element of the neurovascular unit, plays an important role in the maintenance of central nervous system homeostasis (Hawkins and Davis, 2005).…”

Erythropoietin Prevents Blood Brain Barrier Damage Induced by Focal Cerebral Ischemia in Mice

“…Similarly, treatment in vitro with recombinant VEGF resulted in an increase in paracellular permeability and a decrease in junctional localization of occludin, an important tight junction protein [7]. In vivo studies showed that blockade of VEGF signaling by treatment with anti-VEGF antibody 1 h before and immediately after middle cerebral artery occlusion (MCAO) significantly rescued BBB leakage, directly implicating VEGF as an important mediator of the early permeability events following ischemic stroke [8].…”

Catalpol stimulates VEGF production via the JAK2/STAT3 pathway to improve angiogenesis in rats’ stroke model

“…VEGF enhances angiogenesis, but worsens rather than improves cerebral hemodynamics after stroke (Wang et al, 2005). Low-dose VEGF treatment aggravates hemorrhagic transformation (Chi et al, 2007;Kanazawa et al, 2011). Inhibition of endogenous VEGF by topical application of an anti-VEGF antibody in the ischemic cortex decreased blood-brain barrier (BBB) disruption (Zhang et al, 2000).…”