Oophorectomy Reduces Estradiol Levels and Long-Term Spontaneous Neurovascular Recovery in a Female Rat Model of Focal Ischemic Stroke
Although epidemiological evidence suggests significant sex and gender-based differences in stroke risk and recovery, females have been widely under-represented in preclinical stroke research. The neurovascular sequelae of brain ischemia in females, in particular, are largely uncertain. We set out to...
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doaj-8c5713addc2c423ca0cdcd3a11297ac02020-11-25T01:12:30ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-09-011110.3389/fnmol.2018.00338400782Oophorectomy Reduces Estradiol Levels and Long-Term Spontaneous Neurovascular Recovery in a Female Rat Model of Focal Ischemic StrokePaolo Bazzigaluppi0Conner Adams1Margaret M. Koletar2Adrienne Dorr3Aleksandra Pikula4Peter L. Carlen5Bojana Stefanovic6Bojana Stefanovic7Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaSunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaSunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaSunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaAdult Vascular Neurology, Toronto Western Hospital, Toronto, ON, CanadaFundamental Neurobiology, Krembil Research Institute, Toronto, ON, CanadaSunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaDepartment of Medical Biophysics, University of Toronto, Toronto, ON, CanadaAlthough epidemiological evidence suggests significant sex and gender-based differences in stroke risk and recovery, females have been widely under-represented in preclinical stroke research. The neurovascular sequelae of brain ischemia in females, in particular, are largely uncertain. We set out to address this gap by a multimodal in vivo study of neurovascular recovery from endothelin-1 model of cortical focal-stroke in sham vs. ovariectomized female rats. Three weeks post ischemic insult, sham operated females recapitulated the phenotype previously reported in male rats in this model, of normalized resting perfusion but sustained peri-lesional cerebrovascular hyperreactivity. In contrast, ovariectomized (Ovx) females showed reduced peri-lesional resting blood flow, and elevated cerebrovascular responsivity to hypercapnia in the peri-lesional and contra-lateral cortices. Electrophysiological recordings showed an attenuation of theta to low-gamma phase-amplitude coupling in the peri-lesional tissue of Ovx animals, despite relative preservation of neuronal power. Further, this chronic stage neuronal network dysfunction was inversely correlated with serum estradiol concentration. Our pioneering data demonstrate dramatic differences in spontaneous recovery in the neurovascular unit between Ovx and Sham females in the chronic stage of stroke, underscoring the importance of considering hormonal-dependent aspects of the ischemic sequelae in the development of novel therapeutic approaches and patient recruitment in clinical trials.https://www.frontiersin.org/article/10.3389/fnmol.2018.00338/fullarterial spin labelingestrogenischemiaovariectomylocal field potential |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Paolo Bazzigaluppi Conner Adams Margaret M. Koletar Adrienne Dorr Aleksandra Pikula Peter L. Carlen Bojana Stefanovic Bojana Stefanovic |
spellingShingle |
Paolo Bazzigaluppi Conner Adams Margaret M. Koletar Adrienne Dorr Aleksandra Pikula Peter L. Carlen Bojana Stefanovic Bojana Stefanovic Oophorectomy Reduces Estradiol Levels and Long-Term Spontaneous Neurovascular Recovery in a Female Rat Model of Focal Ischemic Stroke Frontiers in Molecular Neuroscience arterial spin labeling estrogen ischemia ovariectomy local field potential |
author_facet |
Paolo Bazzigaluppi Conner Adams Margaret M. Koletar Adrienne Dorr Aleksandra Pikula Peter L. Carlen Bojana Stefanovic Bojana Stefanovic |
author_sort |
Paolo Bazzigaluppi |
title |
Oophorectomy Reduces Estradiol Levels and Long-Term Spontaneous Neurovascular Recovery in a Female Rat Model of Focal Ischemic Stroke |
title_short |
Oophorectomy Reduces Estradiol Levels and Long-Term Spontaneous Neurovascular Recovery in a Female Rat Model of Focal Ischemic Stroke |
title_full |
Oophorectomy Reduces Estradiol Levels and Long-Term Spontaneous Neurovascular Recovery in a Female Rat Model of Focal Ischemic Stroke |
title_fullStr |
Oophorectomy Reduces Estradiol Levels and Long-Term Spontaneous Neurovascular Recovery in a Female Rat Model of Focal Ischemic Stroke |
title_full_unstemmed |
Oophorectomy Reduces Estradiol Levels and Long-Term Spontaneous Neurovascular Recovery in a Female Rat Model of Focal Ischemic Stroke |
title_sort |
oophorectomy reduces estradiol levels and long-term spontaneous neurovascular recovery in a female rat model of focal ischemic stroke |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2018-09-01 |
description |
Although epidemiological evidence suggests significant sex and gender-based differences in stroke risk and recovery, females have been widely under-represented in preclinical stroke research. The neurovascular sequelae of brain ischemia in females, in particular, are largely uncertain. We set out to address this gap by a multimodal in vivo study of neurovascular recovery from endothelin-1 model of cortical focal-stroke in sham vs. ovariectomized female rats. Three weeks post ischemic insult, sham operated females recapitulated the phenotype previously reported in male rats in this model, of normalized resting perfusion but sustained peri-lesional cerebrovascular hyperreactivity. In contrast, ovariectomized (Ovx) females showed reduced peri-lesional resting blood flow, and elevated cerebrovascular responsivity to hypercapnia in the peri-lesional and contra-lateral cortices. Electrophysiological recordings showed an attenuation of theta to low-gamma phase-amplitude coupling in the peri-lesional tissue of Ovx animals, despite relative preservation of neuronal power. Further, this chronic stage neuronal network dysfunction was inversely correlated with serum estradiol concentration. Our pioneering data demonstrate dramatic differences in spontaneous recovery in the neurovascular unit between Ovx and Sham females in the chronic stage of stroke, underscoring the importance of considering hormonal-dependent aspects of the ischemic sequelae in the development of novel therapeutic approaches and patient recruitment in clinical trials. |
topic |
arterial spin labeling estrogen ischemia ovariectomy local field potential |
url |
https://www.frontiersin.org/article/10.3389/fnmol.2018.00338/full |
work_keys_str_mv |
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