Cerebral Aneurysm as an Exacerbating Factor in Stroke Pathology and a Therapeutic Target for Neuroprotection

Naoki      Tajiri; Tsz      Lau; Loren      E. Glover; Kazutaka      Shinozuka; Yuji      Kaneko; Harry      van Loveren; Cesar      V. Borlongan

Abstract

Stroke remains a major cause of death in the US and around the world. Despite major scientific advances in our understanding of stroke pathology, the only FDA-approved drug for ischemic stroke is tissue plasminogen activator (tPA). Moreover, the therapeutic window for tPA is confined to the acute phase of stroke, thereby greatly limiting its benefits to less than 3% of ischemic stroke patients. Many treatment strategies for stroke have targeted the subacute or chronic phase in an effort to abrogate the secondary cell death that ensues after the initial stroke insult. Here, we advance the hypothesis that blood vessel disruption, or aneurysm, in the brain is an exacerbating factor for stroke, especially in the evolution of the penumbra or peri-infarct area. A better understanding of aneurysm, specifically its dynamic onset and juxtaposition to the ischemic brain tissue should facilitate the development of novel strategies for attenuating the secondary cell death associated with stroke. To this end, we discuss the laboratory and clinical evidence implicating aneurysm formation in stroke and also provide insights on how stem cell therapy may prove efficacious in combating aneurysm and stroke.

Keywords: Stroke, aneurysm, stem cell therapy, angiogenesis, vasculogenesis, tissue plasminogen activator (tPA), blood vessel disruption, ischemic brain tissue, secondary cell death, peri-infarct area.