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 indicates that different molecules afford protection from ischemic neurodegeneration, but all clinical trials conducted so far have inexorably failed....

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Bibliographic Details
Published in:The FEBS journal 2009-01, Vol.276 (1), p.36-45
Main Authors: Moroni, Flavio, Chiarugi, Alberto
Format: Article
Language:English
Subjects:
Biochemistry
blood brain barrier
Brain damage
Brain Damage, Chronic - drug therapy
Brain Damage, Chronic - etiology
Brain Damage, Chronic - genetics
Brain Damage, Chronic - pathology
Brain Ischemia - complications
Brain Ischemia - drug therapy
Brain Ischemia - genetics
Brain Ischemia - pathology
Cell Death
Cerebrovascular Circulation
Clinical Trials as Topic
Collateral Circulation
endothelium
Humans
inflammation
ischemia
microglia
Molecular biology
neuroglia
Neurology
Neurons - pathology
neuroprotection
Neuroprotective Agents - therapeutic use
neurovascular unit
PARP-1
pericytes
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerase Inhibitors
Poly(ADP-ribose) Polymerases - drug effects
Poly(ADP-ribose) Polymerases - physiology
Receptors, N-Methyl-D-Aspartate - physiology
Stroke
Stroke - drug therapy
Stroke - pathology
Transcriptional Activation
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Summary: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.
ISSN:1742-464X
1742-4658
DOI:10.1111/j.1742-4658.2008.06768.x