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Int. J. Mol. Sci. 2018, 19(10), 3124; https://doi.org/10.3390/ijms19103124

Sex-Dependent Effects of Bmal1-Deficiency on Mouse Cerebral Cortex Infarction in Response to Photothrombotic Stroke

1
Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Merowinger Platz 1A, 40225 Düsseldorf, Germany
2
Institute for Pathology, University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 4 September 2018 / Revised: 1 October 2018 / Accepted: 3 October 2018 / Published: 11 October 2018
(This article belongs to the Special Issue Neuroprotective Strategies 2018)
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Abstract

Stroke is a leading cause of disability and death worldwide. There is increasing evidence that occurrence of ischemic stroke is affected by circadian system and sex. However, little is known about the effect of these factors on structural recovery after ischemic stroke. Therefore, we studied infarction in cerebral neocortex of male and female mice with deletion of the clock gene Bmal1 (Bmal1−/−) after focal ischemia induced by photothrombosis (PT). The infarct core size was significantly smaller 14 days (d) as compared to seven days after PT, consistent with structural recovery during the sub-acute phase. However, when sexes were analyzed separately 14 days after PT, infarct core was significantly larger in wild-type (Bmal1+/+) female as compared to male Bmal1+/+ mice, and in female Bmal1+/+, as compared to female Bmal1−/− mice. Volumes of reactive astrogliosis and densely packed microglia closely mirrored the size of infarct core in respective groups. Estradiol levels were significantly higher in female Bmal1−/− as compared to Bmal1+/+ mice. Our data suggests a sex-dependent effect and an interaction between sex and genotype on infarct size, the recruitment of astrocytes and microglia, and a relationship of these cells with structural recovery probably due to positive effects of estradiol during the subacute phase. View Full-Text
Keywords: Bmal1; clock gene; photothrombotic stroke; cortical infarcts; reactive astrogliosis; activated microglia Bmal1; clock gene; photothrombotic stroke; cortical infarcts; reactive astrogliosis; activated microglia
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Lembach, A.; Stahr, A.; Ali, A.A.H.; Ingenwerth, M.; von Gall, C. Sex-Dependent Effects of Bmal1-Deficiency on Mouse Cerebral Cortex Infarction in Response to Photothrombotic Stroke. Int. J. Mol. Sci. 2018, 19, 3124.

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