Proestrus levels of estradiol during transient global cerebral ischemia improves the histological outcome of the hippocampal CA1 region: perfusion-dependent and-independent mechanisms

He, Zhen; He, Yun Ju; Day, Arthur L.; Simpkins, James W.

doi:10.1016/s0022-510x(01)00648-7

Cited by 68 publications

(49 citation statements)

References 42 publications

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“…Numerous studies have shown that female sex and administration of estrogen are associated with neuroprotection after focal and global cerebral ischemia (Alkayed et al, 1998;He et al, 2002;Hurn and Macrae, 2000;Jover et al, 2002), although one study reported an opposite effect of estrogen (Harukuni et al, 2001). In our WT mice, we observed a sex-linked neuroprotective effect in hippocampus, but not in caudoputamen.…”

Section: Discussionmentioning

confidence: 99%

SOD1 Overexpression and Female Sex Exhibit Region-Specific Neuroprotection after Global Cerebral Ischemia Due to Cardiac Arrest

Kofler

Hurn

Traystman

2005

J Cereb Blood Flow Metab

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Cardiac arrest is often associated with poor neurologic outcome since therapeutic options are limited. We tested the hypothesis that overexpression of CuZn superoxide dismutase (SOD þ /À) is neuroprotective in a new murine model of cardiac arrest and cardiopulmonary resuscitation (CPR). Second, we investigated if female and male mice sustain similar injury and if sex-specific outcomes are altered by SOD overexpression. Neuronal injury was quantified 3 days after 8 mins of KClinduced cardiac arrest by calculating the percentage of ischemic neurons for caudoputamen and hippocampal CA1 region. In rostral caudoputamen, less neuronal cell loss was found for SOD þ /À mice (31%722%) when compared with wild-type (WT) mice (47%731%, Po0.05). Superoxide dismutase overexpression did not reduce injury in the caudal caudoputamen. No sex-linked protection was evident in either genotype in the caudoputamen. Female WT mice had less CA1 injury than male WT mice (26%731% versus 54%730%, Po0.05), whereas no sex difference was found in SOD þ /À mice (female: 42%729%; male: 37%737%). Comparison of hippocampal injury between genotypes revealed no differences for either males or females. In conclusion, SOD1 overexpression and female sex were associated with significant neuroprotection in this murine cardiac arrest model. However, no additive neuroprotection was observed, and these beneficial effects were restricted to specific brain regions.

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Section: Discussionmentioning

confidence: 99%

SOD1 Overexpression and Female Sex Exhibit Region-Specific Neuroprotection after Global Cerebral Ischemia Due to Cardiac Arrest

Kofler

Hurn

Traystman

2005

J Cereb Blood Flow Metab

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“…Following our first report of neuroprotection with estrogens in an animal model of ischemia (Simpkins et al, 1997a, we and other have demonstrated that estrogens protects the brain from ischemic damage induced by transient cerebral ischemia (Alkayed et al, 1998;Rusa et al, 1999;Hurn and Macrae, 2000;Shi et al, 2001,Sampei et al, 2000, permanent cerebral ischemia (Dubal et al, 1998Yang et al, 2001), subarachnoid hemorrhage , and global ischemia (He et al, 2002). The protective effects of estrogens are seen with 17β-estradiol, as well as non-feminizing estrogens, such as 17α-estradiol , ENT-estradiol , and 2-adamantyl-estrone (Liu et al, 2002).…”

Section: Estrogens and Neuroprotectionmentioning

confidence: 93%

Estrogen actions on mitochondria—Physiological and pathological implications

Simpkins

Yang

Sarkar

et al. 2008

Molecular and Cellular Endocrinology

135

105

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Estrogens are potent neuroprotective hormones and mitochondria are the site of cellular life-death decisions. As such, it is not surprising that we and other have shown that estrogens have remarkable effects on mitochondrial function. Herein we provide evidence for a primary effect of estrogens on mitochondrial function, achieved in part by the import of estrogen receptor β (ERβ) into the mitochondria where it mediates a number of estrogen actions on this vital organelle. ERβ is imported into the mitochondria, through tethering to cytosolic chaperone protein and/or through direct interaction with mitochondrial import proteins. In the mitochondria, ERβ can affect transcription of critical mitochondrial genes through the interaction with estrogen response elements (ERE) or through protein-protein interactions with mitochondrially imported transcription factors. The potent effects of estrogens on mitochondrial function, particularly during mitochondrial stress, argues for a role of estrogens in the treatment of mitochondrial defects in chronic neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD) and more acute conditions of mitochondrial compromise, like cerebral ischemia and traumatic brain injury.

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Section: Nih Public Accessmentioning

confidence: 99%

“…When administered before the onset of focal ischemia, estradiol significantly reduces the volume of the resultant infarct in both male (Toung et al, 1998) and female (Dubal et al, 1998) rats. Similarly, when administered prior to the onset of transient global ischemia, estradiol significantly protects against the characteristic cell death that occurs in the pyramidal cell layer of the CA1 region of the hippocampus (Gulinello et al, 2006;He et al, 2002;Jover et al, 2002;Miller et al, 2005;Shughrue and Merchenthaler, 2003).The extent to which ischemia-induced cell loss is related to impairments in cognition and the degree to which estradiol-mediated neuroprotection translates into preservation of behavioral function are not well understood. Transient global ischemia results in severe impairments in performance on hippocampally-dependent spatial learning tasks such as the Morris water maze (Block and Schwarz, 1997,1998;Hagan and Beaughard, 1990;Jaspers et al, 1990;Nelson et al, 1997;Nunn et al, 1994;Olsen et al, 1994;Wright et al, 1996).…”

mentioning

confidence: 99%

Acute pretreatment with estradiol protects against CA1 cell loss and spatial learning impairments resulting from transient global ischemia

Sandstrom

Rowan

2007

Hormones and Behavior

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Estradiol can act to protect against hippocampal damage resulting from transient global ischemia, but little is known about the functional consequences of such neuroprotection. The present study examines whether acute estradiol administered prior to the induction of transient global ischemia protects against hippocampal cell death and deficits in performance on a spatial learning task. Ovariectomized female rats were primed with estradiol benzoate or oil vehicle 48 and 24 hrs prior to experiencing one of three durations of 4-vessel occlusion (0, 5, or 10 min). Performance on the cued and hidden platform versions of the Morris water maze was assessed one week following ischemia. On the cued platform task, neither hormone treatment nor ischemia significantly influenced acquisition. When tested on the hidden platform task, however, oil-treated rats exhibited impairments in spatial learning after either 5 or 10 min of ischemia while estradiol-treated rats showed no impairments after 5 min of ischemia and only mild impairments after 10 min of ischemia. Immediately following behavioral testing, rats were perfused and survival of CA1 pyramidal cells was assessed. Ischemia was associated with the loss of CA1 pyramidal cells but rats that received estradiol prior to ischemia showed less severe damage. Furthermore, the extent of cell loss was correlated with degree of spatial bias expressed on a probe trial following hidden platform training. These findings indicate that acute exposure to estradiol prior to ischemia is both neuroprotective and functionally protective. Keywords estrogen; ischemia; cardiac arrest; hippocampus; neuroprotection; spatial learning; water maze Acute pretreatment with estradiol protects against CA1 cell loss and spatial learning impairments resulting from transient global ischemiaTransient global ischemia leads to the dramatic loss of neurons in the CA1 region of the hippocampus in humans (Horn and Schlote, 1992;Tanabe et al., 1999;Taraszewska et al., 2002), non-human primates (Zola-Morgan et al., 1992), and rodents (Pulsinelli et al., 1982). This neuronal damage can be accompanied by severe impairments in cognition. For example, human survivors of ischemic strokes typically exhibit disruptions in performance on tasks requiring attention, learning and memory (Elwan et al., 1994;Volpe et al., 1986; Address Correspondence to: Noah J. Sandstrom, Department of Psychology, Williams College, 18 Hoxsey Street, Williamstown, MA 01267, Phone: 413-597-4107, Fax: 413-597-2085, E-mail: Noah.Sandstrom@williams.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain...

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Proestrus levels of estradiol during transient global cerebral ischemia improves the histological outcome of the hippocampal CA1 region: perfusion-dependent and-independent mechanisms

Cited by 68 publications

References 42 publications

SOD1 Overexpression and Female Sex Exhibit Region-Specific Neuroprotection after Global Cerebral Ischemia Due to Cardiac Arrest

SOD1 Overexpression and Female Sex Exhibit Region-Specific Neuroprotection after Global Cerebral Ischemia Due to Cardiac Arrest

Estrogen actions on mitochondria—Physiological and pathological implications

Acute pretreatment with estradiol protects against CA1 cell loss and spatial learning impairments resulting from transient global ischemia

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