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

Protection of the brain following cerebral ischemia through the attenuation of PARP-1-induced... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

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

Loading next page...
 
/lp/elsevier/protection-of-the-brain-following-cerebral-ischemia-through-the-Y4kNojyB0h
Publisher
Elsevier
Copyright
Copyright © 2015 Elsevier B.V.
ISSN
0006-8993
D.O.I.
10.1016/j.brainres.2015.07.023
Publisher site
See Article on Publisher Site

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.

Journal

Brain ResearchElsevier

Published: Oct 22, 2015

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off