TY - JOUR
T1 - Poststroke cognitive impairment and hippocampal neurovascular remodeling
T2 - The impact of diabetes and sex
AU - Ward, Rebecca
AU - Valenzuela, John Paul
AU - Li, Weiguo
AU - Dong, Guangkuo
AU - Fagan, Susan C.
AU - Ergul, Adviye
N1 - Funding Information:
A. Ergul is a Research Career Scientist at the Charlie Norwood Veterans Affairs (VA) Medical Center (Augusta, Georgia). This work was supported in part by VA Merit Award BX000347, a VA Research Career Scientist Award, and National Institutes of Health (NIH) Grants R01-NS-083559 and PO1-HL-128207 (to A. Ergul); VA Merit Award BX000891 and NIH Grant R21-NS-063965 (to S. C. Fagan); and American Heart Association Predoctoral Fellowship 17PRE33660400 (to R. Ward).
Publisher Copyright:
© 2018 the American Physiological Society.
PY - 2018/10/29
Y1 - 2018/10/29
N2 - 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.
AB - 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.
KW - Blood vessels
KW - Cognition
KW - Memory
KW - Neurodegeneration
KW - Type 2 diabetes
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U2 - 10.1152/ajpheart.00390.2018
DO - 10.1152/ajpheart.00390.2018
M3 - Article
AN - SCOPUS:85055894975
SN - 0363-6135
VL - 315
SP - H1402-H1413
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5
ER -
