Angiogenesis.pdf

Acta Neuropathol (2009) 117:481–496 DOI 10.1007/s00401-009-0483-6 REVIEW Angiogenesis after cerebral ischemia Heike Beck · Karl H. Plate Received: 7 November 2008 / Revised: 8 January 2009 / Accepted: 8 January 2009 / Published online: 14 January 2009 ? Springer-Verlag 2009 Abstract Though the vascular system of the adult brain is extremely stable under normal baseline conditions, endothelial cells start to proliferate in response to brain ischemia. The induction of angiogenesis, primarily in the ischemic boundary zone, enhances oxygen and nutri- ent supply to the aVected tissue. Additionally, the gener- ation of new blood vessels facilitates highly coupled neurorestorative processes including neurogenesis and synaptogenesis which in turn lead to improved func- tional recovery. To take advantage of angiogenesis as a therapeutic concept for stroke treatment, the knowledge of the precise molecular mechanisms is mandatory. Especially, since a couple of growth factors involved in post-ischemic angiogenesis may have detrimental adverse eVects in the brain by increasing vascular per- meability. This article summarizes the knowledge of molecular mechanisms of angiogenesis following cerebral ischemia. Finally, experimental pharmacological and cellular approaches to stimulate and enhance post-ischemic angio- genesis are discussed. Keywords Stroke · Angiogenesis · Neurorestorative treatment For several decades, most attempts to treat stroke were focused on neuroprotection [34]. However, only one FDA approved drug for the treatment of clinical ische- mic stroke, recombinant tissue plasminogen activator, shows therapeutic eVect when given very early in care- fully selected patients [164]. At present, scientists inten- siWed their work on pharmacological approaches beyond the hyperacute phase of stroke. The time window for therapies improving stroke recovery, so called neurore- storative therapies, is likely to be far longer than that for acute neuroprotection [20]. Neurorest