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The Journal of Biomedical Research 2022年第5期36卷 353-357页

作者： Xi Yan Junkui Shang Runrun Wang Fengyu Wang Jiewen Zhang Department of Neurology Henan Provincial People's HospitalZhengzhou University People's HospitalHenan University People's HospitalZhengzhouHenan 450003China

cerebral small vessel disease (CSVD) is a leading cause of stroke and dementia. As the most common type of inherited CSVD, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by the NOTCH3 gene mutation which leads to Notch3 ectodomain deposition and extracellular matrix aggregation around the small vessels. It further causes smooth muscle cell degeneration and small vessel arteriopathy in the central nervous system. Compromised cerebral blood flow occurs in the early stage of CADASIL and is associated with white matter hyperintensity, the typical neuroimaging pathology of CADASIL. This suggests that cerebral hypoperfusion may play an important role in the pathogenesis of CADASIL. However, the mechanistic linkage between NOTCH3 mutation and cerebral hypoperfusion remains unknown. Therefore, in this mini-review, it examines the cellular and molecular mechanisms contributing to cerebral hypoperfusion in CADASIL.

关键词： cerebral hypoperfusion CADASIL Notch3 mural cell astrocyte

Blood-brain barrier pathology in cerebral small vessel disease

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Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma Solé-Guardia Amanda J.Kiliaan Department of Medical Imaging Anatomy Radboud University Medical Center Donders Institute for Brain Cognition & Behavior Center for Medical Neuroscience Preclinical Imaging Center PRIME Radboud Alzheimer Center

cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly. Although at first it was considered innocuous, small vessel disease is nowadays regarded as one of the major vascular causes of dementia. Radiological signs of small vessel disease include small subcortical infarcts, white matter magnetic resonance imaging hyperintensities, lacunes, enlarged perivascular spaces, cerebral microbleeds, and brain atrophy; however, great heterogeneity in clinical symptoms is observed in small vessel disease patients. The pathophysiology of these lesions has been linked to multiple processes, such as hypoperfusion, defective cerebrovascular reactivity, and blood-brain barrier dysfunction. Notably, studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease. Therefore, the purpose of this review is to provide a new foundation in the study of small vessel disease pathology. First, we discuss the main structural domains and functions of the blood-brain barrier. Secondly, we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease. Finally, we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

Chronic hypoperfusion due to intracranial large artery stenosis is not associated with cerebralβ-amyloid deposition and brain atrophy

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Chinese Medical Journal 2022年第5期135卷 591-597页

作者： Dongyu Fan Huiyun Li Dongwan Chen Yang Chen Xu Yi Heng Yang Qianqian Shi Fangyang Jiao Yi Tang Qiming Li Fangyang Wang Shunan Wang Rongbing Jin Fan Zeng Yanjiang Wang Department of Neurology and Centre for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing400042China Institute of Brain and Intelligence Third Military Medical UniversityChongqing400038China Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing400042China Shigatse Branch Xinqiao HospitalThird Military Medical UniversityTibet 857012China Department of Nuclear Medicine Daping HospitalThird Military Medical UniversityChongqing400042China Department of Radiology Daping HospitalThird Military Medical UniversityChongqing400042China

Background:Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease(AD).However,there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD *** investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in ***:We enrolled a group of cognitively normal patients(median age:64 years)with unilateral chronic cerebral *** of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion.11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each ***:The median age of the 10 participants,consisting of 4 males and 6 females,was 64 years(47-76 years).We found that there were no differences in standard uptake ratios of the cortex(volume of interest[VOI]:P=0.721,region of interest[ROI]:P=0.241)and grey/white ratio(VOI:P=0.333,ROI:P=0.445)and brain atrophy indices(Bicaudate,Bifrontal,Evans,Cella,Cella media,and Ventricular index,P>0.05)between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral ***:Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebralβ-amyloid deposition and neurodegeneration in humans.

关键词： cerebral hypoperfusion β-amyloid Brain atrophy Alzheimer disease

Effects of different regional cerebral blood flow on white matter hyperintensity in CADASIL patients

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The Journal of Biomedical Research 2022年第5期36卷 368-374页

作者： Runrun Wang Jiewen Zhang Junkui Shang Fengyu Wang Xi Yan Department of Neurology Henan Provincial People's HospitalZhengzhou University People's HospitalHenan University People's HospitalZhengzhouHenan 450003China

cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is an early-onset inherited small vessel *** cerebral blood flow(CBF)may contribute to white matter hyperintensity(WMH)severity in CADASIL,but more evidence is needed to support this *** study comprised six patients with CADASIL who harbored mutations in the coding sequence of NOTCH3 and twelve age-matched neurologically healthy *** collected clinical and imaging data from patients with CADASIL and divided the brain into four regions:WMH,normal-appearing white matter(NAWM),gray matter(GM),and global *** analyzed the relationship between CBF of each region and the WMH *** with the control group,CBF was significantly decreased in all four regions in the CADASIL *** CBF in these regions was correlated with higher WMH volume in *** in the NAWM,GM and global regions was positively correlated with that in WMH ***,after correction tests,only CBF in the WMH region but not in NAWM,GM and global regions was associated with WMH *** findings suggest that CBF in the WMH region is an influencing factor of the WMH severity in CADASIL.

关键词： cerebral hypoperfusion neurovascular unit white matter hyperintensity small vessel disease CADASIL

PRELIMINARY STUDY OF OMENTUM TRANSPOSITION TO BRAIN FOR TREATMENT OF ALZHEIMER’S DISEASE

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Journal of Shanghai Second Medical University(Foreign Language Edition) 2007年第1期19卷 46-51页

作者：仲骏吴伟烈 Harry Goldsmith Department of Neurosurgery Xinhua Hospital Shanghai JiaoTong University School of Medicine Department of Surgery University of Nevada School of Medicine Reno NV89413 USA

Objective To learn the effect of omemtum transposition to the brain of patients with Alzheimer’s disease. Methods Ten consecutive patients, aged 58-81 years old, underwent graft of their elongated pedicled omentum onto their left frontal-temperal-parietal cerebral cortex. Those patients, who had more than five years of dementia with low mini mental-state examination (MMSE) scores of 2-15, were diagnosed by a neurologist. All subjects underwent single photon evoked computer tomography (SPECT) pre- and post-operatively. SPECT results were analyzed semi-quantitatively by calculation of the left/right radioactivity counts symmetry index (Si). The patients were followed up to one year. The outcome was evaluated by the neurologist with a modified scale of activities of daily living (mADL) as well as the MMSE. Results Three months following the surgery, the Si of SPECT increased from (98.7±1.9)% to (103.9±2.3)% (P=0.0307). The neurological and neuropsychological testing scores increased insignificantly during the follow-up period. By the one year, the MMSE score rose from 8.7±1.4 to 10.7±1.8(P>0.05), while the mADL from 13.3±1.8 to 16.9±2.0 (P>0.05). One of the patients suffered a heart attack, two had epileptic episodes postoperatively. Conclusion We believe that omental transposition to the brain augments cerebral blood flow, which might be helpful to decelerate the processing of Alzheimer’s disease. However, it is still a potentially risky procedure for the elderly.

关键词： Alzheimer's disease cerebral blood flow cerebral hypoperfusion omentum transposition