 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
The Journal of Neuroscience, December 10, 2003, 23(36):11420-11426
Previous Article | Next Article
Development/Plasticity/Repair
Estradiol Attenuates Programmed Cell Death after Stroke-Like Injury
Shane W. Rau,1 Dena B. Dubal,3 Martina Böttner,2 Lynnette M. Gerhold,2 andPhyllis M. Wise2 1Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536, 2Department of Neurobiology, Physiology, and Behavior, Division of Biological Sciences, University of California, Davis, Davis, California 95616, and 3Department of Neurology, University of California at San Francisco, San Francisco, California 94143
Estradiol is a known neurotrophic and neuroprotective factor. Our previous work demonstrated that replacement with physiological concentrations of estradiol protects the cortex against middle cerebral artery occlusion (MCAO)-induced cell death. The cerebral cortex exhibits caspase-dependent programmed cell death (PCD) in many models of focal cerebral ischemia. We hypothesized that estradiol attenuates PCD during stroke injury. The current study explored the temporospatial pattern of markers of PCD, their relationship to the evolution of injury, and their modulation by estradiol. Rats were ovariectomized and treated with either estradiol or vehicle. One week later, rats underwent MCAO, and brains were collected at 1, 4, 8, 16, and 24 hr. We assessed the temporospatial evolution of infarction volume, DNA fragmentation, and levels of spectrin cleavage products in ischemic cortex. Estradiol led to a delay and attenuation of injury-mediated DNA fragmentation as early as 8 hr after MCAO. Estradiol also dramatically reduced the level of the 120 kDa caspase-mediated spectrin breakdown product (SBDP120) at 4 hr but not at 8 or 16 hr. The SBDP150, produced by caspase and calpain, showed peak levels at 16 hr but was not altered by estradiol. These results strongly suggest that estradiol protects the ischemic cortex by attenuating PCD, thereby reducing caspase activity, DNA fragmentation, and subsequently, overall cell death. These studies deepen our understanding of the mechanisms underlying estrogen-mediated neuroprotection.
Key words: apoptosis; ischemia; stroke; middle cerebral artery occlusion; TUNEL; estrogen (estradiol); caspase
Received May 29, 2003; revised October 8, 2003; accepted October 16, 2003.
This article has been cited by other articles:
T. I. Lam, P. M. Wise, and M. E. O'Donnell
Cerebral microvascular endothelial cell Na/H exchange: evidence for the presence of NHE1 and NHE2 isoforms and regulation by arginine vasopressin
Am J Physiol Cell Physiol, August 1, 2009; 297(2): C278 - C289.
[Abstract] [Full Text] [PDF]
E. Kilic, A. Spudich, U. Kilic, K. M. Rentsch, R. Vig, C. M. Matter, H. Wunderli-Allenspach, J.-M. Fritschy, C. L. Bassetti, and D. M. Hermann
ABCC1: a gateway for pharmacological compounds to the ischaemic brain
Brain, October 1, 2008; 131(10): 2679 - 2689.
[Abstract] [Full Text] [PDF]
E. Chang, M. E. O'Donnell, and A. I. Barakat
Shear stress and 17{beta}-estradiol modulate cerebral microvascular endothelial Na-K-Cl cotransporter and Na/H exchanger protein levels
Am J Physiol Cell Physiol, January 1, 2008; 294(1): C363 - C371.
[Abstract] [Full Text] [PDF]
S. M Johnson, M. Maleki-Dizaji, J. A Styles, and I. N H White
Ishikawa cells exhibit differential gene expression profiles in response to oestradiol or 4-hydroxytamoxifen
Endocr. Relat. Cancer, June 1, 2007; 14(2): 337 - 350.
[Abstract] [Full Text] [PDF]
S. Suzuki, C. M. Brown, C. D. Dela Cruz, E. Yang, D. A. Bridwell, and P. M. Wise
Timing of estrogen therapy after ovariectomy dictates the efficacy of its neuroprotective and antiinflammatory actions
PNAS, April 3, 2007; 104(14): 6013 - 6018.
[Abstract] [Full Text] [PDF]
L. B. J. Morales, K. K. Loo, H.-b. Liu, C. Peterson, S. Tiwari-Woodruff, and R. R. Voskuhl
Treatment with an estrogen receptor alpha ligand is neuroprotective in experimental autoimmune encephalomyelitis.
J. Neurosci., June 21, 2006; 26(25): 6823 - 6833.
[Abstract] [Full Text] [PDF]
D. B. Dubal, S. W. Rau, P. J. Shughrue, H. Zhu, J. Yu, A. B. Cashion, S. Suzuki, L. M. Gerhold, M. B. Bottner, S. B. Dubal, et al.
Differential Modulation of Estrogen Receptors (ERs) in Ischemic Brain Injury: A Role for ER{alpha} in Estradiol-Mediated Protection against Delayed Cell Death
Endocrinology, June 1, 2006; 147(6): 3076 - 3084.
[Abstract] [Full Text] [PDF]
E. Vegeto, S. Belcredito, S. Ghisletti, C. Meda, S. Etteri, and A. Maggi
The Endogenous Estrogen Status Regulates Microglia Reactivity in Animal Models of Neuroinflammation
Endocrinology, May 1, 2006; 147(5): 2263 - 2272.
[Abstract] [Full Text] [PDF]
A S Chagin, D Chrysis, M Takigawa, E M Ritzen, and L Savendahl
Locally produced estrogen promotes fetal rat metatarsal bone growth; an effect mediated through increased chondrocyte proliferation and decreased apoptosis
J. Endocrinol., February 1, 2006; 188(2): 193 - 203.
[Abstract] [Full Text] [PDF]
C. D. Toran-Allerand, A. A. Tinnikov, R. J. Singh, and I. S. Nethrapalli
17{alpha}-Estradiol: A Brain-Active Estrogen?
Endocrinology, September 1, 2005; 146(9): 3843 - 3850.
[Abstract] [Full Text] [PDF]
E. R. Levin
Integration of the Extranuclear and Nuclear Actions of Estrogen
Mol. Endocrinol., August 1, 2005; 19(8): 1951 - 1959.
[Abstract] [Full Text] [PDF]
C. B. Huppenbauer, L. Tanzer, L. L. DonCarlos, and K. J. Jones
Gonadal Steroid Attenuation of Developing Hamster Facial Motoneuron Loss by Axotomy: Equal Efficacy of Testosterone, Dihydrotestosterone, and 17-{beta} Estradiol
J. Neurosci., April 20, 2005; 25(16): 4004 - 4013.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|