Rinsho Shinkeigaku (Clinical Neurology)


VEGF-A therapeutic target against hemorrhagic transformation after t-PA treatment-

Masato Kanazawa, M.D., Ph.D.1), Tetsuya Takahashi, M.D., Ph.D.2), Kunio Kawamura, M.D., Ph.D.3) and Takayoshi Shimohata, M.D., Ph.D.4)

1)Department of Neurology, Brain Research Institute, Niigata University
2)Department of Neurology, National Hospital Organization Nishiniigata Chuo Hospital
3)Department of Rehabilitation, Midori Hospital
4)Department of Neurology, Gifu University Graduate School of Medicine

Tissue plasminogen activator (t-PA) treatment is beneficial for patients with ischemic stroke within 4.5 h of stroke onset, because the risk of intracerebral hemorrhagic transformation (HT) increases with delayed t-PA treatment. The benefits of t-PA thrombolysis are heavily dependent on time to treatment. Development of vasoprotective drugs that attenuate HT after delayed t-PA treatment might improve the prognosis of stroke patients and extend the therapeutic time window of t-PA and endovascular thrombolysis. An angiogenic factor, vascular endothelial growth factor (VEGF), might be associated with the blood-brain barrier (BBB) disruption after focal cerebral ischemia. By using a rat thromboembolic model, delayed t-PA treatment at 4 h after ischemia promoted expression of VEGF in BBB, matrix metalloproteinase-9 (MMP-9) activation, degradation of BBB components, and HT. We demonstrated that HT was inhibited by intravenous administration of an anti-VEGF neutralizing antibody/VEGF receptor antagonist. In addition, for clinical application, reverse translation studies, a path from bedside to bench, are necessary.
Full Text of this Article in Japanese PDF (724K)

(CLINICA NEUROL, 59: 699|706, 2019)
key words: cerebral ischemia, t-PA, hemorrhagic transformation, vascular protection, vascular endothelial growth factor

(Received: 15-Jul-19)