This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shi, J. Articles by Simpkins, J. W. Search for Related Content PubMed PubMed Citation Articles by Shi, J. Articles by Simpkins, J. W. Related Collections Computerized tomography and Magnetic Resonance Imaging Neuroprotectors

(Stroke. 2001;32:987.)
© 2001 American Heart Association, Inc.

Original Contributions

Estrogens Decrease Reperfusion-Associated Cortical Ischemic Damage

An MRI Analysis in a Transient Focal Ischemia Model

Jiong Shi, MD, PhD; Jonathan D. Bui, BS; Shao-Hua Yang, MD; Zhen He, MD, PhD; Timothy H. Lucas, BS; David L. Buckley, PhD; Stephen J. Blackband, PhD; Michael A. King, PhD; Arthur L. Day, MD James W. Simpkins, PhD

From the Departments of Pharmacodynamics (J.S., J.W.S.), Neurosurgery (S-H.Y., Z.H., T.H.L., A.L.D.), Neuroscience (M.A.K.), and Center for Structural Biology (J.D.B., D.L.B., S.J.B.), University of Florida Brain Institute (J.S., J.D.B., S-H.Y., Z.H., T.H.L., D.L.B., S.J.B., M.A.K., A.L.D., J.W.S.), University of Florida, Gainesville, and National High Magnetic Field Laboratory, Tallahassee, Fla (S.J.B.).

Background and Purpose—Early identification of irreversible cerebral ischemia is critical in defining strategies that influence neuronal survival after stroke. We used MRI to investigate the effects of 17ß-estradiol (E2) on the temporal evolution of focal ischemia.

Methods—Female rats were ovariectomized and divided into 1 of 2 groups: ovariectomy alone (OVX; n=4) or ovariectomy with estrogen replacement (OVX+E2; n=3). Both groups were then subjected to 1-hour middle cerebral artery occlusion (MCAO), with the use of a standardized endovascular monofilament model, followed by reperfusion. Sequential diffusion-weighted (DWI) and T2-weighted (T2WI) MRI were obtained during and after the MCAO. In separate groups of animals (n=5 for OVX and OVX+E2), cerebral blood flow (CBF) was measured by laser-Doppler methods before, during, and after occlusion.

Results—DWI detected similar lesion characteristics during MCAO in both groups. In the OVX group, lesion size did not change during reperfusion, but the signal intensity ratio increased early and stabilized during the latter stages. In contrast, DWI lesion size decreased during reperfusion in OVX+E2 rats by 50% to 60% (P<0.05), a size reduction almost exclusively limited to cortical regions. During MCAO, the signal intensity ratio in OVX+E2 rats was reduced compared with OVX rats. Reperfusion further attenuated the signal intensity ratio in cortical but not subcortical regions (P<0.05 versus OVX). T2WI revealed no lesions in either group during MCAO, but it detected lesion sizes similar to that of DWI during reperfusion. Furthermore, similar patterns and magnitudes of estrogen treatment–related decrease in lesion size were noted after reperfusion. T2WI demonstrated less intense signal intensity ratio changes in both groups compared with DWI. There were no differences in CBF between groups either during occlusion, early reperfusion, or 1 day after reperfusion.

Conclusions—This study strongly suggests that estrogens selectively protect cortical tissue from ischemic damage during MCAO and that this protection is exerted during both the occlusion and reperfusion phases of ischemia and does not involve an estrogen-related change in CBF.

Key Words: cerebral ischemia, focal • estrogens • magnetic resonance imaging • neuroprotection • reperfusion injury

This article has been cited by other articles:

				D. A. Schreihofer, K. D. Do, and A. M. Schreihofer High-soy diet decreases infarct size after permanent middle cerebral artery occlusion in female rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R103 - R108. [Abstract] [Full Text] [PDF]

				M. E. Jung, M. B. Gatch, and J. W. Simpkins Estrogen Neuroprotection Against the Neurotoxic Effects of Ethanol Withdrawal: Potential Mechanisms Experimental Biology and Medicine, January 1, 2005; 230(1): 8 - 22. [Abstract] [Full Text] [PDF]

				G. E. Hoffman and S. L. Zup Good Versus Evil: Changing the Approach to Hormone Replacement Therapy Endocrinology, November 1, 2003; 144(11): 4698 - 4699. [Full Text] [PDF]

				L. Prokai, K. Prokai-Tatrai, P. Perjesi, A. D. Zharikova, E. J. Perez, R. Liu, and J. W. Simpkins Quinol-based cyclic antioxidant mechanism in estrogen neuroprotection PNAS, September 30, 2003; 100(20): 11741 - 11746. [Abstract] [Full Text] [PDF]

				S. Kaja, S.-H. Yang, J. Wei, K. Fujitani, R. Liu, A.-M. Brun-Zinkernagel, J. W. Simpkins, K. Inokuchi, and P. Koulen Estrogen Protects the Inner Retina from Apoptosis and Ischemia-Induced Loss of Vesl-1L/Homer 1c Immunoreactive Synaptic Connections Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 3155 - 3162. [Abstract] [Full Text] [PDF]

				S.-H. Yang, E. Perez, J. Cutright, R. Liu, Z. He, A. L. Day, and J. W. Simpkins Testosterone increases neurotoxicity of glutamate in vitro and ischemia-reperfusion injury in an animal model J Appl Physiol, January 1, 2002; 92(1): 195 - 201. [Abstract] [Full Text] [PDF]