Cerebral microhemorrhages (CMHs; microbleeds), which are small focal intracerebral hemorrhages, importantly contribute to the pathogenesis of cognitive decline and dementia in older adults. Although recently it has been increasingly recognized that the venous side of the cerebral circulation likely plays a fundamental role in the pathogenesis of a wide spectrum of cerebrovascular and brain disorders, its role in the pathogenesis of CMHs has never been studied. The present study was designed to experimentally test the hypothesis that venous congestion can exacerbate the genesis of CMHs. Increased cerebral venous pressure was induced by internal and external jugular vein ligation (JVL) in C57BL/6 mice in which systemic hypertension was induced by treatment with angiotensin II plus L-NAME. Histological analysis (diaminobenzidine staining) showed that mice with JVL developed multiple CMHs. CMHs in mice with JVL were often localized adjacent to veins and venules and their morphology was consistent with venous origin of the bleeds. In brains of mice with JVL, a higher total count of CMHs was observed compared to control mice. CMHs were distributed widely in the brain of mice with JVL, including the cortical gray matter, brain stem, the basal ganglia, subcortical white matter, cerebellum, and the hippocampi. In mice with JVL, there were more CMHs predominantly in cerebral cortex, brain stem, and cerebellum than in control mice. CMH burden, defined as total CMH volume, also significantly increased in mice with JVL. Thus, cerebral venous congestion can exacerbate CMHs. These observations have relevance to the pathogenesis of cognitive impairment associated with right heart failure as well as elevated cerebral venous pressure due to jugular venous reflux in older adults.

脑微出血 (CMHs; microbleeds) 是小的局灶性脑内出血，对老年人认知能力下降和痴呆的发病机制有重要贡献。尽管最近人们越来越认识到脑循环的静脉侧可能在广泛的脑血管和脑部疾病的发病机制中起着重要作用，但它在 CMHs 发病机制中的作用从未被研究过。本研究旨在通过实验检验静脉充血会加剧 CMHs 发生的假设。在 C57BL/6 小鼠中，通过血管紧张素 II 加 L-NAME 治疗诱发全身性高血压，颈内静脉和颈外静脉结扎术 (JVL) 可引起脑静脉压升高。组织学分析（二氨基联苯胺染色）表明，患有 JVL 的小鼠出现了多个 CMH。JVL 小鼠的 CMHs 通常位于静脉和小静脉附近，其形态与出血的静脉来源一致。在 JVL 小鼠的大脑中，与对照小鼠相比，观察到更高的 CMH 总数。CMHs 广泛分布于 JVL 小鼠的大脑中，包括皮质灰质、脑干、基底神经节、皮质下白质、小脑和海马。在 JVL 小鼠中，与对照小鼠相比，主要在大脑皮层、脑干​​和小脑中存在更多的 CMH。CMH 负担，定义为总 CMH 体积，在 JVL 小鼠中也显着增加。因此，脑静脉充血会加剧 CMHs。