Protection of the brain following cerebral ischemia through the attenuation of PARP-1-induced neurovascular unit damage in rats

Abstract Cerebral ischemia is a major health crisis throughout the world, and the currently available thrombolytic therapy is unsatisfactory. Cell death following cerebral ischemia is mediated by a complex pathophysiological interaction of various mechanisms. During an ischemic insult, not only neurons but all of the components of the neurovascular unit, such as glia, endothelia, pericytes and basal membranes, are destroyed. Previous studies have shown that excessive stimulation of poly (ADP-ribose) polymerase (PARP-1) is crucial for cerebral injury after ischemic insult, which is an important cause of cell death in all cell types within the neurovascular unit. To investigate whether PARP-1 plays an important role in protecting the neurovascular unit following cerebral ischemia, we evaluated neurobehavioral deficits, PARP-1 activity, blood brain barrier (BBB) disruption and neurovascular unit deficits using Western blot analysis, TTC staining and electron microscopy in an MCAO rat model. The results revealed that PARP-1 enzymatic activity was dramatically increased after ischemia. Inhibition of PARP-1 significantly reduced the extent of both cerebral infarction and edema, improved neurological scores, and attenuated the damage to the neurovascular unit in cerebral ischemia. Collectively, these findings demonstrate that the down-regulation of PARP-1 activity contributes to reducing post-ischemic brain damage via protection of the neurovascular unit.