Background. Microangiopathy-related cerebral damage (MARCD) is an entity of cerebrovascular disease based on arteriosclerosis in deep white matter, whi

Recently, a genome-wide screen has shown a major quantitative trait locus (QTL) for a stroke-associated phenotype on rat chromosome 1 (RNO1) independent of QTL for blood pressure (BP) in the stroke-prone spontaneously hypertensive rat (SHRSP) of a Heidelberg colony. However, it remains to be elucidated whether these observations reflect the existence of different genes predisposing to each of the disorders. To address this issue, we performed comprehensive approaches in a Japanese colony, Izm, as follows. First, we undertook genome-wide searches in F ₁ (SHRSP/Izm×WKY/Izm)×SHRSP/Izm back-cross (n=63) to pursue a causal relation between hypertension and stroke. Although the strongest linkage to BP (LOD score of 3.4) was identified on RNO1, its relevance to stroke was not supported in the F ₁ back-cross studied. Second, we also investigated linkage to BP in F ₂ progeny (n=175) involving the stroke-resistant (or normal) spontaneously hypertensive rat (SHR). In F ₂ studies of SHR/Izm, this locus did not appear to constitute a principal BP QTL. Third, we constructed congenic animals with detailed phenotype characterization. Transfer of a chromosomal fragment between markers Klk1 and D1Rat116 from WKY/Izm onto the SHRSP/Izm background lowered systolic BP by 20 to 80 mm Hg, prevented development of apparent stroke, and exaggerated impaired glucose tolerance. In conclusion, we have successfully isolated an RNO1 region affecting BP, stroke, and glucose tolerance in SHRSP/Izm-derived congenic rats. The size of the introgressed region is large, but our novel congenic strain should help delineate complex, genetic impairments underlying BP and associated vascular disease phenotypes.

Several experimental studies have indicated that nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) exert detrimental effects on ischemic brain tissue; Nox-knockout mice generally exhibit resistance to damage due to experimental stroke following middle cerebral artery occlusion (MCAO). Furthermore, our previous MCAO study indicated that infarct size and blood-brain barrier breakdown are enhanced in mice with pericyte-specific overexpression of Nox4, relative to levels observed in controls. However, it remains unclear whether Nox affects the stroke outcome directly by increasing oxidative stress at the site of ischemia, or indirectly by modifying physiological variables such as blood pressure or cerebral blood flow (CBF). Because of technical problems in the measurement of physiological variables and CBF, it is often difficult to address this issue in mouse models due to their small body size; in our previous study, we examined the effects of Nox activity on focal ischemic injury in a novel congenic rat strain: stroke-prone spontaneously hypertensive rats with loss-of-function in Nox. In this review, we summarize the current literature regarding the role of Nox in focal ischemic injury and discuss critical issues that should be considered when investigating Nox-related pathophysiology in animal models of stroke.

Given that public transportation networks are less developed in rural than in urban areas, a lack of accessibility to dental care facilities could be a barrier to routine dental checkups. Thus, we hypothesized that the distance to the dental care facilities is a risk factor for tooth loss. The aim of this study was to test whether there is an association between the distance to dental care facilities, estimated by geographic information systems, and number of teeth, assessed by an oral examination, among elderly residents of a rural area in Japan. Data were collected in 2016 from a cross-sectional study conducted in Shimane prefecture, Japan. After excluding participants with missing data (n = 21), we analyzed data from 710 participants. Of them, 40.6% were male and the mean (standard deviation) age was 67.4 (7.4) years. Further, 68.0% (n = 483) had at least 20 teeth. We found that the distance to dental care facilities was significantly associated with the number of teeth (less than 20) (odds ratio = 1.07, 95% confidence interval = 1.01–1.12) after adjustment for potential confounders. This result suggested that individuals without easy access to dental care facilities may be important targets for dental care.