TAILIEUCHUNG - Báo cáo khoa học: Post-ischemic brain damage: targeting PARP-1 within the ischemic neurovascular units as a realistic avenue to stroke treatment

Stroke is the third leading cause of death in industrialized countries but efficacious stroke treatment is still an unmet need. Preclinical research indi-cates that different molecules afford protection from ischemic neurodegen-eration, but all clinical trials conducted so far have inexorably failed. | MINIREVIEW Post-ischemic brain damage targeting PARP-1 within the ischemic neurovascular units as a realistic avenue to stroke treatment Flavio Moroni and Alberto Chiarugi Department of Preclinicaland ClinicalPharmacology University of Florence Italy Keywords blood brain barrier endothelium inflammation ischemia microglia neuroprotection neurovascular unit PARP-1 pericytes stroke Correspondence F. Moroni Dipartimento di Farmacologia Viale Pieraccini 6 50139 Firenze Italy Fax 39 055 4271226 Tel 39 055 4271280 E-mail Received 3 July 2008 revised 11 September 2008 accepted 14 October 2008 Stroke is the third leading cause of death in industrialized countries but efficacious stroke treatment is still an unmet need. Preclinical research indicates that different molecules afford protection from ischemic neurodegeneration but all clinical trials conducted so far have inexorably failed. Critical re-evaluation of experimental data shows that all the components of the neurovascular unit such as neurons glia endothelia and basal membranes must be protected during the ischemic insult to obtain substantial and long-lasting neuroprotection. Here we propose the nuclear enzyme poly ADP-ribose polymerase PARP-1 as a key effector of cell death in the various elements of the neurovascular units and assert that drugs inhibiting PARP-1 may therefore represent valuable tools for pharmacological treatment of stroke patients. doi Therapeutic strategies aimed at reducing brain damage after ischemic stroke have been a major focus of academic and industrial research for the past 30 years. Two primary therapeutic approaches have been intensively studied the first can be defined as the vascular approach and its main goal is the rapid re-opening of occluded blood vessels so that oxygen and nutrients may return to the ischemic region. The second may be defined as the cellular approach and is based on the possibility of interfering with the

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