NDLI: Effects of Androgens on Early Post-ischemic Neurogenesis in Mice

Content Provider	Springer Nature Link
Author	Zhang, Wenri Cheng, Jian Vagnerova, Kamila Ivashkova, Yulia Young, Jennifer Cornea, Anda Grafe, Marjorie R. Murphy, Stephanie J. Hurn, Patricia D. Brambrink, Ansgar M.
Copyright Year	2013
Abstract	Although androgens are reported to affect stroke outcomes by altering ischemic tissue damage, their effect on post-injury repair is unknown. Since neurogenesis has recently been recognized as contributing to stroke outcomes, we investigated the role of androgens on stroke-induced neurogenesis. Adult male mice were subjected to transient middle cerebral artery occlusion (MCAO) and neurogenesis was examined 1 week later by quantifying BrdU/doublecortin-positive and BrdU/NeuN-positive neurons in brain germinal regions as well as the injured striatum. To elucidate the role of endogenous androgens, post-MCAO neurogenesis was examined in gonadally intact males, intact males implanted with the androgen receptor antagonist flutamide, and surgically castrated males. Surgical castration or pharmacologic androgen receptor blockade had no effects on post-ischemic neurogenesis, except that continuous androgen receptor blockade unexpectedly suppressed maturation of newborn neurons (BrdU/NeuN-positive cells) in the dentate gyrus. Post-MCAO neurogenesis was also examined in surgically castrated mice treated with continuous release implants containing testosterone or dihydrotestosterone (DHT). Testosterone and DHT robustly inhibited post-ischemic neurogenesis in the dentate gyrus, and the more potent androgen DHT virtually abolished the presence of immature newborn neurons (BrdU/doublecortin-positive cells) in the injured striatum. Our data suggest that endogenous androgens do not alter post-stroke neurogenesis quantitatively, but the presence of supra-physiological androgen stimulation profoundly suppresses early neurogenesis in germinal brain areas and reduces cellular repair in injured tissue after cerebral ischemia. These results advance the understanding of the role that androgens play in stroke outcomes.
Starting Page	301
Ending Page	311
Page Count	11
File Format	PDF
ISSN	18684483
Journal	Translational Stroke Research
Volume Number	5
Issue Number	2
e-ISSN	1868601X
Language	English
Publisher	Springer US
Publisher Date	2013-11-11
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Androgens Testosterone Dihydrotestosterone Androgen receptor Neurogenesis Cerebral ischemia Neurosciences Neurology Cardiology Neurosurgery Vascular Surgery
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Neuroscience Neurology (clinical)

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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