Poststroke cognitive impairment and hippocampal neurovascular remodeling: the impact of diabetes and sex
Diabetes increases the risk and severity of cognitive impairment, especially after ischemic stroke. Pathological remodeling of the cerebrovasculature has been postulated to contribute to poor neuronal repair and worsened cognitive deficits in diabetes. However, little is known about the effect of di...
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| Published in | American journal of physiology. Heart and circulatory physiology Vol. 315; no. 5; pp. H1402 - H1413 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Physiological Society
01.11.2018
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| Series | Sex Differences in Cardiovascular and Cerebrovascular Physiology, Disease, and Signaling Mechanisms |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Diabetes increases the risk and severity of cognitive impairment, especially after ischemic stroke. Pathological remodeling of the cerebrovasculature has been postulated to contribute to poor neuronal repair and worsened cognitive deficits in diabetes. However, little is known about the effect of diabetes on the vascularization of hippocampus, a domain critical to memory and learning. Therefore, we had two aims for this study: 1) to determine the impact of diabetes on hippocampal neurovascular remodeling and the resulting cognitive impairment after stroke using two models with varying disease severity, and 2) to compare the effects of ischemia on hippocampal neurovascular injury in diabetic male and female animals. Stroke was induced by middle cerebral artery occlusion (MCAO) by either the suture or embolic method in control and diabetic age-matched male and female Wistar rats. Hippocampal neuronal density, vascular architecture, and microglial activation as well as cognitive outcomes were measured. Embolic MCAO induced greater neuronal degeneration, pathological vascularization, microglial activation, and cognitive impairment in diabetes as compared with control animals or 60-min MCAO. Although diabetic males had lower neuronal density at baseline, diabetic females had more neurodegeneration after stroke. Control animals recovered cognitive function by day 14 after stroke; diabetic animals showed deficits regardless of sex. These results suggest that mechanisms underlying cognitive decline in diabetes may differ in males and females and provide further insight to the impact of diabetes on stroke severity and poststroke cognitive impairment. NEW & NOTEWORTHY The present study is the first to provide comparative information on the effects of diabetes and ischemia on cognitive outcomes in both sexes while also evaluating the neurovascular structure in the hippocampus, a critical region for cognitive and memory-related tasks. |
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| AbstractList | Diabetes increases the risk and severity of cognitive impairment, especially after ischemic stroke. Pathological remodeling of the cerebrovasculature has been postulated to contribute to poor neuronal repair and worsened cognitive deficits in diabetes. However, little is known about the effect of diabetes on the vascularization of hippocampus, a domain critical to memory and learning. Therefore, we had two aims for this study: 1) to determine the impact of diabetes on hippocampal neurovascular remodeling and the resulting cognitive impairment after stroke using two models with varying disease severity, and 2) to compare the effects of ischemia on hippocampal neurovascular injury in diabetic male and female animals. Stroke was induced by middle cerebral artery occlusion (MCAO) by either the suture or embolic method in control and diabetic age-matched male and female Wistar rats. Hippocampal neuronal density, vascular architecture, and microglial activation as well as cognitive outcomes were measured. Embolic MCAO induced greater neuronal degeneration, pathological vascularization, microglial activation, and cognitive impairment in diabetes as compared with control animals or 60-min MCAO. Although diabetic males had lower neuronal density at baseline, diabetic females had more neurodegeneration after stroke. Control animals recovered cognitive function by day 14 after stroke; diabetic animals showed deficits regardless of sex. These results suggest that mechanisms underlying cognitive decline in diabetes may differ in males and females and provide further insight to the impact of diabetes on stroke severity and poststroke cognitive impairment. NEW & NOTEWORTHY The present study is the first to provide comparative information on the effects of diabetes and ischemia on cognitive outcomes in both sexes while also evaluating the neurovascular structure in the hippocampus, a critical region for cognitive and memory-related tasks. Diabetes increases the risk and severity of cognitive impairment, especially after ischemic stroke. Pathological remodeling of the cerebrovasculature has been postulated to contribute to poor neuronal repair and worsened cognitive deficits in diabetes. However, little is known about the effect of diabetes on the vascularization of hippocampus, a domain critical to memory and learning. Therefore, we had two aims for this study: 1 ) to determine the impact of diabetes on hippocampal neurovascular remodeling and the resulting cognitive impairment after stroke using two models with varying disease severity, and 2 ) to compare the effects of ischemia on hippocampal neurovascular injury in diabetic male and female animals. Stroke was induced by middle cerebral artery occlusion (MCAO) by either the suture or embolic method in control and diabetic age-matched male and female Wistar rats. Hippocampal neuronal density, vascular architecture, and microglial activation as well as cognitive outcomes were measured. Embolic MCAO induced greater neuronal degeneration, pathological vascularization, microglial activation, and cognitive impairment in diabetes as compared with control animals or 60-min MCAO. Although diabetic males had lower neuronal density at baseline, diabetic females had more neurodegeneration after stroke. Control animals recovered cognitive function by day 14 after stroke; diabetic animals showed deficits regardless of sex. These results suggest that mechanisms underlying cognitive decline in diabetes may differ in males and females and provide further insight to the impact of diabetes on stroke severity and poststroke cognitive impairment. NEW & NOTEWORTHY The present study is the first to provide comparative information on the effects of diabetes and ischemia on cognitive outcomes in both sexes while also evaluating the neurovascular structure in the hippocampus, a critical region for cognitive and memory-related tasks. Diabetes increases the risk and severity of cognitive impairment, especially after ischemic stroke. Pathological remodeling of the cerebrovasculature has been postulated to contribute to poor neuronal repair and worsened cognitive deficits in diabetes. However, little is known about the effect of diabetes on the vascularization of hippocampus, a domain critical to memory and learning. Therefore, we had two aims for this study: 1) to determine the impact of diabetes on hippocampal neurovascular remodeling and the resulting cognitive impairment after stroke using two models with varying disease severity, and 2) to compare the effects of ischemia on hippocampal neurovascular injury in diabetic male and female animals. Stroke was induced by middle cerebral artery occlusion (MCAO) by either the suture or embolic method in control and diabetic age-matched male and female Wistar rats. Hippocampal neuronal density, vascular architecture, and microglial activation as well as cognitive outcomes were measured. Embolic MCAO induced greater neuronal degeneration, pathological vascularization, microglial activation, and cognitive impairment in diabetes as compared with control animals or 60-min MCAO. Although diabetic males had lower neuronal density at baseline, diabetic females had more neurodegeneration after stroke. Control animals recovered cognitive function by day 14 after stroke; diabetic animals showed deficits regardless of sex. These results suggest that mechanisms underlying cognitive decline in diabetes may differ in males and females and provide further insight to the impact of diabetes on stroke severity and poststroke cognitive impairment. NEW & NOTEWORTHY The present study is the first to provide comparative information on the effects of diabetes and ischemia on cognitive outcomes in both sexes while also evaluating the neurovascular structure in the hippocampus, a critical region for cognitive and memory-related tasks. |
| Author | Dong, Guangkuo Ergul, Adviye Valenzuela, John Paul Fagan, Susan C Li, Weiguo Ward, Rebecca |
| Author_xml | – sequence: 1 givenname: Rebecca orcidid: 0000-0001-6752-5600 surname: Ward fullname: Ward, Rebecca organization: Departments of Neuroscience and Regenerative Medicine, Augusta University , Augusta, Georgia – sequence: 2 givenname: John Paul surname: Valenzuela fullname: Valenzuela, John Paul organization: Department of Physiology, Augusta University , Augusta, Georgia – sequence: 3 givenname: Weiguo surname: Li fullname: Li, Weiguo organization: Charlie Norwood Veterans Administration Medical Center , Augusta, Georgia – sequence: 4 givenname: Guangkuo surname: Dong fullname: Dong, Guangkuo organization: Center for Pharmacy and Experimental Therapeutics, University of Georgia College of Pharmacy , Augusta, Georgia – sequence: 5 givenname: Susan C surname: Fagan fullname: Fagan, Susan C organization: Center for Pharmacy and Experimental Therapeutics, University of Georgia College of Pharmacy , Augusta, Georgia – sequence: 6 givenname: Adviye surname: Ergul fullname: Ergul, Adviye organization: Charlie Norwood Veterans Administration Medical Center , Augusta, Georgia |
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| Snippet | Diabetes increases the risk and severity of cognitive impairment, especially after ischemic stroke. Pathological remodeling of the cerebrovasculature has been... |
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| SubjectTerms | Activation Animals Behavior, Animal Cerebral blood flow Cognition Cognition Disorders - etiology Cognition Disorders - physiopathology Cognition Disorders - psychology Cognitive ability Cognitive tasks Degeneration Density Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - chemically induced Diabetes Mellitus, Experimental - complications Diet, High-Fat Female Females Health risks Hippocampus Hippocampus - blood supply Hippocampus - pathology Hippocampus - physiopathology Impairment Infarction, Middle Cerebral Artery - complications Infarction, Middle Cerebral Artery - physiopathology Infarction, Middle Cerebral Artery - psychology Ischemia Learning Male Males Memory Memory tasks Microglia - pathology Neovascularization, Pathologic Nerve Degeneration Neurodegeneration Neurons - pathology Occlusion Rats, Wistar Recovery of Function Risk Factors Sex Sex Factors Streptozocin Stroke Time Factors Vascularization |
| Title | Poststroke cognitive impairment and hippocampal neurovascular remodeling: the impact of diabetes and sex |
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