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Yao H.,Center for Emotional and Behavioral Disorders | Nabika T.,The University of Shimane
Journal of Translational Medicine | Year: 2012

We reviewed the early development of various focal ischemia models in spontaneously hypertensive rats (SHR), and summarized recent reports on this topic. Among 6 focal ischemia models established in divergent substrains of SHR, distal middle cerebral artery occlusion is the most frequently used and relevant method of focal ischemia in the light of penumbra concept. We performed an online PubMed search (2001-2010), and identified 118 original articles with focal ischemia in SHR. Physiological parameters such as age, body weight, and even blood pressure were often neglected in the literature: the information regarding the physiological parameters of SHR is critical, and should be provided within the methodology section of all articles related to stroke models in SHR. Although the quality of recent studies on neuroprotective strategy is improving, the mechanisms underlying the protection should be more clearly recognized so as to facilitate the translation from animal studies to human stroke. To overcome the genetic heterogeneity in substrains of SHR, new approaches, such as a huge repository of genetic markers in rat strains and the congenic strategy, are currently in progress. © 2012 Yao and Nabika; licensee BioMed Central Ltd. Source


Fukuda K.,Kurume University | Takashima Y.,Center for Emotional and Behavioral Disorders | Hashimoto M.,Center for Emotional and Behavioral Disorders | Uchino A.,Saitama University | And 2 more authors.
Journal of Stroke and Cerebrovascular Diseases | Year: 2014

Our previous study showed that the male predominance of silent brain infarction (SBI) was largely because of higher prevalence of alcohol habit and smoking in men than in women. In the present study, we further conducted an analysis of brain magnetic resonance imaging findings to examine whether early menopause contributes to SBI in community-dwelling subjects. Women were queried as to the age and cause of menopause, the total number of children, and the age at giving birth to her last child. Among 306 female subjects aged 60 years or older, univariate analysis showed that early menopause (total or natural) was significantly associated with SBI but age at natural menopause, number of children, and age at the last parity were not. In the total of 715 subjects (283 men and 432 women with a mean age of 67.2 years), the forward stepwise method of logistic analysis revealed that natural early menopause (odds ratio [OR] 4.28, 95% confidence interval [CI] 1.07-17.11), in addition to age, hypertension, alcohol intake, and smoking, was a significant factor concerning SBI. Also in the subgroup of female subjects aged 60 years or older, natural early menopause was a significant factor concerning SBI (OR 4.35, 95% CI 1.05-18.08) adjusted for covariates. Although the prevalence of natural early menopause was low (3.3% of 306 female subjects), natural menopause before the age of 40 years may be a risk for SBI or small-vessel disease of the brain. © 2014 by National Stroke Association. Source


Takashima Y.,Center for Emotional and Behavioral Disorders | Mori T.,Center for Emotional and Behavioral Disorders | Hashimoto M.,Center for Emotional and Behavioral Disorders | Kinukawa N.,Center for Emotional and Behavioral Disorders | And 3 more authors.
Journal of Stroke and Cerebrovascular Diseases | Year: 2011

We performed brain gradient-echo T2*-weighted magnetic resonance imaging (GE-MRI) in community-dwelling healthy people to investigate the clinical correlates (i.e., possible risk factors) and cognitive function in subjects with cerebral microbleeds (MBs). We examined 368 healthy subjects age 39 years or older living in a Japanese rural community, performing baseline and clinical assessments and brain MRI (T2*-weighted, T1-weighted, T2-weighted, and FLAIR). We assessed global cognitive function in subjects age 60 years or older using the Mini-Mental State Examination (MMSE). An MMSE score >1.5 standard deviations (SD) below the mean score for a particular age group was considered subnormal. MBs were present in 14 of 368 subjects overall (3.8%; 11 males and 3 females) and in 14 of 225 subjects age ≥60 years (6.2%). In a logistic regression analysis, older age (odds ratio [OR] = 2.649/10 years; 95% confidence interval [CI] = 1.465-4.788) and male sex (OR = 6.876; 95% CI = 1.801-26.248) were significantly related to the presence of MBs. The presence of silent brain infarction and white matter lesions was correlated with MBs, suggesting that MBs were the consequence of small-vessel diseases. There was a significant association between the presence of MBs and subnormal cognition defined by MMSE (OR = 5.226; 95% CI = 1.463-18.662). Our data suggest that in healthy community-dwelling subjects, MBs may be a consequence of small-vessel disease, which is correlated with aging, male sex, and subnormal cognition. © 2011 by National Stroke Association. Source


Yao H.,Center for Emotional and Behavioral Disorders | Takashima Y.,Center for Emotional and Behavioral Disorders | Araki Y.,University of Shizuoka | Uchino A.,Saitama University | And 2 more authors.
Journal of Stroke and Cerebrovascular Diseases | Year: 2015

Background: Although physical inactivity is a major public health problem, the causative factors for physical inactivity per se are poorly understood. To address this issue, we investigated the relationship between deep white matter lesions (DWMLs) on magnetic resonance imaging, apathy, and physical activities using structural equation modeling (SEM). Methods: We examined 317 community-dwelling elderly subjects (137 men and 180 women with a mean age of 64.5 years) without dementia or clinically apparent depression. Physical activity was assessed with a questionnaire consisting of 3 components (leisure-time, work, and sport activities). Results: The mean score from the apathy scale (a visual analogue version of Starkstein's apathy scale) of the Grades 2-3 DWML group was 420 (95% confidence interval [CI] 379-461), which was lower (more apathetic) than the Grade 0 DWML group score of 478 (95% CI 463-492) after adjustment for education as a covariate. SEM showed that the direct paths from DWMLs or education to apathy were significant, and the direct path from apathy to leisure-time activity was highly significant (β=.25, P<.001). The degree of apathetic behavior was negatively associated with sport activity in female subjects and positively associated with TV watching in male subjects. Conclusions: The results of the study show that DWMLs are one of the major factors that cause apathetic behavior and that apathy has significant negative effects on leisure-time physical activity in community-dwelling elderly subjects. Even a minor level of apathy without major depression would have a significant impact on activities of daily living and quality of life. © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved. Source


Yao H.,Center for Emotional and Behavioral Disorders | Miwa Y.,Kyushu University | Takashima Y.,Center for Emotional and Behavioral Disorders | Yahara K.,Kurume University | And 5 more authors.
Hypertension Research | Year: 2011

Although recent studies have found that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment in population-based cohorts, the mechanisms of cognitive impairment in subjects with CKD are unclear. We examined 503 elderly subjects (mean age: 72.4 years), who were living independently at home without apparent dementia, using MRI. The subject was judged as having frontal lobe dysfunction if the scores on the modified Stroop test were higher than the fifth quintile for each given decade. Serum creatinine values, measured by the enzymatic method, were used for the Japanese equation of estimated glomerular filtration rate (eGFR). Subjects in the frontal lobe dysfunction group tended to have higher blood pressure, lower eGFR and more lacunar infarcts, and were less educated. When possible confounders were entered into the multivariate logistic regression model, the independent predictors of frontal lobe dysfunction were eGFR (odds ratio 0.854; 95% confidence interval (CI) 0.743-0.983 per 10 ml min -1 per 1.73 m 2) and the number of lacunar infarction (odds ratio 1.460; 95% CI 1.127-1.892). The mean of the logarithmically transformed Stroop test scores in the eGFR<60 ml min -1 per 1.73 m 2 group was 1.376 (95% CI 1.301-1.451), which was significantly higher than that (1.250) for the eGFR 60-89 ml min -1 per 1.73 m 2 group (95% CI 1.215-1.285) (P=0.009) and tended to be higher than that (1.264) for the eGFR 90 ml min -1 per 1.73 m 2 group (95% CI 1.188-1.340) (analysis of covariance, adjusted for age). The present study showed that CKD and subclinical lacunar infarction independently contributed to frontal lobe dysfunction in healthy elderly subjects. © 2011 The Japanese Society of Hypertension All rights reserved. Source

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