LOGIN TO YOUR ACCOUNT

Username
Password
Remember Me
Or use your Academic/Social account:

CREATE AN ACCOUNT

Or use your Academic/Social account:

Congratulations!

You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.

Important!

Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message

CREATE AN ACCOUNT

Name:
Username:
Password:
Verify Password:
E-mail:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Kleinschnitz, Christoph; Grund, Henrike; Wingler, Kirstin; E. Armitage, Melanie; Jones, Emma; Mittal, Manish; Barit, David; Schwarz, Tobias; Geis, Christian; Kraft, Peter; Barthel, Konstanze; K. Schuhmann, Michael; M. Herrmann, Alexander; G. Meuth, Sven; Stoll, Guido; Meurer, Sabine; Schrewe, Anja; Becker, Lore; Gailus-Durner, Valérie; Fuchs, Helmut; Klopstock, Thomas; Hrabé de Angelis, Martin; Jandeleit-Dahm, Karin; Shah, Ajay M.; Weissmann, Norbert; H. H. W. Schmidt, Harald (2010)
Publisher: Figshare
Type: dataset
Subjects: oxidase, cardiovascular system, Neuroscience, Physiology, neurodegeneration, inhibition, Medicine, prevents, nadph, Genetics, Pharmacology, induced, oxidative, post-stroke

Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox4−/−) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox4−/− mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy.

Share - Bookmark

Download from

Funded by projects

No projects found

Cite this research data

Collected from