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Gender, Sex Steroids, and Cerebral Ischemic Pathobiology

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

Biological sex is an important genetic determinant of outcome from cerebral ischemia and clinical stroke. Emerging data suggest that sex, as well as reproductive steroids, shapes ischemic cell death in brain. Female sex steroids, the estrogens and progesterone, provide robust neuroprotection in a variety of experimental settings and strongly contribute to sex‐specific responses to ischemia. The purpose of this chapter is: (1) to review the importance of biological sex to ischemic outcome and mechanisms of brain injury, (2) to evaluate the role of female sex steroids as endogenous or exogenous ischemic neuroprotectants, and (3) to review most likely mechanisms by which female sex steroids act to interrupt ischemic cell death pathways.

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Abbreviations

AP1:

activator protein 1

AMPA:

α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid

Ca2+ :

calcium

cAMP:

cyclic adenosine monophosphate

CREB:

cAMP‐responsive element‐binding protein

E14:

embryonic day 14

E2:

estradiol

ER:

estrogen receptors

αERKO:

estrogen receptor deficient knockout mice subtype α

βERKO:

estrogen receptor deficient knockout mice subtype β

ERE:

estrogen‐response elements

GAD:

glutamic acid decarboxylase

i.p.:

intraperitoneal

MCA:

middle cerebral artery

MCAO:

middle cerebral artery occlusion

MAPK:

mitogen‐activated protein kinase

nNOS:

neuronal nitric oxide synthase

NO:

nitric oxide

NMDA:

N‐methyl‐D aspartate

NF‐κB:

nuclear factor‐kappa B

OVX:

ovariectomized

ERK1 and ERK2:

p42/p44 extracellular signal‐regulated kinases 1 and 2

ONOO:

peroxynitrate

PARP‐1:

poly‐ADP ribose polymerase

PR:

progesterone receptor

PKC:

protein kinase C

RSF:

reproductively senescent female

SHRSP:

spontaneously hypertensive stroke prone

SD:

Sprague‐Dawley

TBI:

traumatic brain injury

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  1. I. P. Koerner
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  2. S. J. Murphy
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  3. P. D. Hurn
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, Newyork, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, California, 94305-5487, USA

    Pak H. Chan (Director Neurosurgical Labouratories) (Director Neurosurgical Labouratories)

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Koerner, I.P., Murphy, S.J., Hurn, P.D. (2007). Gender, Sex Steroids, and Cerebral Ischemic Pathobiology. In: Lajtha, A., Chan, P.H. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30383-3_11

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