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The influence of aging on poststroke depression using a rat model via middle cerebral artery occlusion
Authors:Matthew Boyko  Ruslan Kutz  Benjamin F Gruenbaum  Hagit Cohen  Nitsan Kozlovsky  Shaun E Gruenbaum  Yoram Shapira  Alexander Zlotnik
Institution:1. Division of Anesthesiology and Critical Care, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 84101, Israel
4. Division of Anesthesiology and Critical Care, Soroka Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel
2. Beer-Sheva Mental Health Center, The State of Israel Ministry of Health, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
3. Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA
Abstract:Poststroke depression (PSD) is the most frequent psychological sequela following stroke. While previous studies describe the impact of age on brain infarct volume, brain edema, and blood–brain barrier (BBB) breakdown following ischemia, the role of age on PSD has yet to be described. Here, we examine the influence of age on PSD progression in a rat model of PSD by middle cerebral artery occlusion (MCAO). One hundred forty-three rats were divided into three groups. 48 rats 20 weeks of age underwent a sham procedure, 51 rats 20 weeks of age had MCAO, and 44 rats 22–26 months of age had MCAO. Groups were further divided into two subgroups. The first subgroup was used to measure infarct lesion volume, brain edema, and BBB breakdown at 24 h. In the second subgroup at 3 weeks after MCAO, rats were subjected to a sucrose preference test, two-way shuttle avoidance task, forced swimming test, and a brain-derived neurotrophic factor (BDNF) protein level measurement. Total and striatal infarct volume, brain edema, and BBB breakdown in the striatum were increased in older rats, as compared with younger rats. While both old and young rats exhibited depressive-like behaviors on each of the behavioral tests and lower BDNF levels post-MCAO, as compared with control rats, there were no differences between old and young rats. Although older rats suffered from larger infarct volumes, increased brain edema and more BBB disruption following MCAO, the lack of behavioral differences between young and old rats suggests that there was no effect of rat age on the incidence of PSD.
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