title: Effects of androgens on early post-ischemic neurogenesis in mice.
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.
authors: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, UHN-2, Portland, OR, 97239, USA.
authors: Wenri
authors: W
authors: Zhang
authors: Jian
authors: J
authors: Cheng
authors: Kamila
authors: K
authors: Vagnerova
authors: Yulia
authors: Y
authors: Ivashkova
authors: Jennifer
authors: J
authors: Young
authors: Anda
authors: A
authors: Cornea
authors: Marjorie R
authors: MR
authors: Grafe
authors: Stephanie J
authors: SJ
authors: Murphy
authors: Patricia D
authors: PD
authors: Hurn
authors: Ansgar M
authors: AM
authors: Brambrink
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000503:physiopathology; D013196:Dihydrotestosterone / Q000494:pharmacology; D005485:Flutamide / Q000494:pharmacology; D008297:Male; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D020521:Stroke / Q000503:physiopathology*; D013739:Testosterone / Q000494:pharmacology
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D013196:Dihydrotestosterone; D013739:Testosterone; D005485:Flutamide