17β-estradiol pretreatment reduces ca1sector cell death and the spontaneous hyperthermia that follows forebrain ischemia in the gerbil
Section snippets
Animals
All procedures in this study were in accordance with the Canadian Council on Animal Care guidelines as well as international standards, and were approved by a local animal care committee. Efforts were made to minimize animal suffering and to limit the number of animals required.In total, 102 adult male (approximately 75 g on the first surgery day) Mongolian gerbils were used. In experiment 1, these animals were obtained from Charles River (Montreal, QC, Canada) and in experiments 2, 3 and 4
Experiment 1
Baseline Tcore (24 h average on day prior to ISC/sham operation) ranged from 37.3 to 37.4 °C (Group effect: P=0.651). The first 8 h of Tcore following ISC/sham operation (Fig. 1A) were averaged and analyzed by ANOVA (Group effect: P<0.001). During this time the SHAM-E2 (37.2±0.1) and SHAM-NT (37.2±0.1) were not significantly different (P=0.828). Spontaneous hyperthermia occurred in the ISC-NT group (38.1±0.1; P<0.001 versus combined SHAM group: 37.2±0.1). The ISC-E2 group (37.3±0.1) was not
Conclusions
The use of 17β-estradiol, starting 2 weeks prior to ISC, significantly reduced CA1 cell death and concomitant functional abnormalities, as previously found (Hurn et al., 1995; Sudo et al., 1997; Jover et al., 2002; McCullough and Hurn, 2003; Shughrue and Merchenthaler, 2003). Importantly, estrogen blocks the spontaneous postischemic Tcore hyperthermia. Our second experiment suggests that estrogen's neuroprotective effect is solely due to preventing spontaneous hyperthermia because maintenance
Acknowledgments
Research supported by the Canadian Stroke Network. F.C. is the recipient of an Alberta Heritage Foundation for Medical Research medical scholar award. D.L.C. is supported by a summer studentship from the Canadian Stroke Network.
References (36)
- et al.
Characterization of postischemic behavioral deficits in gerbils with and without hypothermic neuroprotection
Brain Res
(1998) - et al.
MK-801 reduces cerebral ischemic injury by inducing hypothermia
Brain Res
(1990) - et al.
Brain temperature measurement in awake and freely moving rodents
Methods
(2003) - et al.
Estrogen raises the sweating threshold in postmenopausal women with hot flashes
Fertil Steril
(2002) - et al.
Proestrus levels of estradiol during transient global cerebral ischemia improves the histological outcome of the hippocampal CA1 region: perfusion-dependent and-independent mechanisms
J Neurol Sci
(2002) Delayed neuronal death in the gerbil hippocampus following ischemia
Brain Res
(1982)- et al.
Estrogen and ischemic neuroprotection: an integrated view
Trends Endocrinol Metab
(2003) - et al.
Hyperthermia nullifies the ameliorating effect of dizocilpine maleate (MK-801) in focal cerebral ischemia
Brain Res
(1995) - et al.
Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome
Lancet
(1996) - et al.
Estrogen prevents the loss of CA1 hippocampal neurons in gerbils after ischemic injury
Neuroscience
(2003)
Limitations of direct estradiol and testosterone immunoassay kits
Steroids
Beta-estradiol protects hippocampal CA1 neurons against transient forebrain ischemia in gerbil
Neurosci Res
Postmenopausal hot flushes: a disorder of thermoregulation
Maturitas
Hyperthermia complicates middle cerebral artery occlusion induced by an intraluminal filament
Brain Res
Hyperthermia delayed by 24 hours aggravates neuronal damage in rat hippocampus following global ischemia
Neurology
Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women
J Appl Physiol
Hypothermia but not the N-methyl-d-aspartate antagonist, MK-801, attenuates neuronal damage in gerbils subjected to transient global ischemia
J Neurosci
Diminished neuronal damage in the rat brain by late treatment with the antipyretic drug dipyrone or cooling following cerebral ischemia
Acta Neuropathol
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