Phosphodiesterase III inhibitor promotes drainage of cerebrovascular β-amyloid

The predominant action of cilostazol on Aβ metabolism is likely to facilitate Aβ clearance due to the sustained cerebrovascular function in vivo. Our findings mechanistically demonstrate that cilostazol is a promising therapeutic approach for AD and CAA

Dysregulation of RNF213 promotes cerebral hypoperfusion

RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rnf213 knockout (KO) and vascular endothelial cell-specific Rnf213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%; p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%; p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role of RNF213 in the maintenance of CBF

哺乳類サーチュインSIRT1による内皮型一酸化窒素合成酵素の脱アセチル化により脳は低灌流傷害への抵抗性を獲得する

京都大学0048新制・課程博士博士(医学)甲第18882号医博第3993号新制||医||1009(附属図書館)31833京都大学大学院医学研究科医学専攻(主査)教授 宮本 享, 教授 小泉 昭夫, 教授 村井 俊哉学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Animal Models of Chronic Cerebral Hypoperfusion: From Mouse to Primate

Vascular cognitive impairment (VCI) or vascular dementia occurs as a result of brain ischemia and represents the second most common type of dementia after Alzheimer’s disease. To explore the underlying mechanisms of VCI, several animal models of chronic cerebral hypoperfusion have been developed in rats, mice, and primates. We established a mouse model of chronic cerebral hypoperfusion by narrowing the bilateral common carotid arteries with microcoils, eventually resulting in hippocampal atrophy. In addition, a mouse model of white matter infarct-related damage with cognitive and motor dysfunction has also been established by asymmetric common carotid artery surgery. Although most experiments studying chronic cerebral hypoperfusion have been performed in rodents because of the ease of handling and greater ethical acceptability, non-human primates appear to represent the best model for the study of VCI, due to their similarities in much larger white matter volume and amyloid β depositions like humans. Therefore, we also recently developed a baboon model of VCI through three-vessel occlusion (both the internal carotid arteries and the left vertebral artery). In this review, several animal models of chronic cerebral hypoperfusion, from mouse to primate, are extensively discussed to aid in better understanding of pathophysiology of VCI

Impact of blood flow volume in determining the destination of intracardiac thrombi using computational fluid dynamics

Atrial fibrillation (AF) induces cardioembolic stroke due to intracardiac fibrin thrombus formation. Although it is well established that a cardioembolic stroke affects the anterior circulation more frequently than it affects the posterior circulation, the destination where the thrombi migrate when cardioembolic stroke occurs in each patient remains unclear. We present a critical case wherein a bilateral internal carotid artery (ICA) territory infarction was diagnosed in a patient with AF who apparently developed nearly simultaneous occlusion in the ICAs bilaterally. A 92-year-old woman with AF who appeared to have developed bilateral occluded common carotid artery (CCA)–ICAs almost simultaneously presented after the sudden onset of coma and quadriplegia and was diagnosed with bilateral ICA territory infarction. The patient died at 4 days after the onset due to the huge infarction. The blood flow in the aorta and the major branches of the aortic arch were examined using computational fluid dynamics (CFD) based on contrast-enhanced computed tomography angiography, which revealed that the right and left CCAs covered larger flow volumes than the other aortic arch branches, suggesting that the intracardiac thrombi migrated into the bilateral CCA–ICAs in the patient. The study findings imply that the fluid dynamic factors of major branches from the aortic arch can be one of the decisive factors for intracardiac thrombus distribution. CFD could simulate patient-specific hemodynamics and may be useful to investigate the susceptibility of the aortic arch branches to occlusion by AF-induced intracardiac emboli

Case report: Near-complete cortical hearing loss caused by sequential development of bilateral putaminal hemorrhage

Intracerebral hemorrhage with sudden hearing loss as the initial symptom is rare. A right-handed man with a history of right putaminal hemorrhage developed near-complete hearing loss and right hemiplegia and was taken to our hospital by ambulance. Non-contrast computed tomography demonstrated acute intracerebral hemorrhage in the left putamen. A region of old right putaminal hemorrhage involving the right temporal stem was also shown on fluid-attenuated inversion recovery. Standard pure-tone audiometry showed right-dominant bilateral sensorineural hearing loss. More than 2 months after onset, the bilateral sensorineural hearing loss gradually improved without interfering with daily life. Detailed history-taking indicated that the old hemorrhage in the right putamen 12 years previously had caused sudden left-dominant bilateral hearing impairment due to asymmetric but bilateral innervation from the auditory nerve. The bilateral damage to the temporal stem involving acoustic radiation resulted in temporary near-complete hearing loss after the recurrence, but the amelioration of edema in the left temporal stem may have resulted in partial recovery of the hearing loss. This patient's clinical progression suggests that the auditory tract ascends mainly on the side opposite the ear and may explain the left dominance in the level of acoustic radiation

Survival rate in the AC group.

<p>(A) Kaplan-Meier method indicates survival rate of mice in the AC group (n = 29). (B) CBF images of the 4 non-surviving mice in the AC group which died during the second week. These mice died on the next day of last CBF measurement.</p