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Clinical and pathological features affecting cardiac sympathetic denervation in autopsy-confirmed dementia with Lewy bodies.
影响尸检证实的路易体痴呆心脏交感神经去神经的临床和病理特征。
- 影响因子:3.37
- DOI:10.1111/ene.14240
- 作者列表:"Takahashi M","Uchihara T","Yoshida M","Wakabayashi K","Kakita A","Takahashi H","Toru S","Orimo S
- 发表时间:2020-04-02
Abstract
BACKGROUND:To clarify the features affecting cardiac sympathetic denervation in autopsy-confirmed dementia with Lewy bodies (DLB) patients. METHODS:Fifty-four autopsy-confirmed DLB patients were enrolled. Tissue samples of the left ventricular anterior wall were immunostained with anti-tyrosine hydroxylase antibody to identify catecholaminergic nerve axons. We quantified immunostained areas as residual cardiac sympathetic nerve (CSN) axons and examined the relationship between the degree of residual CSN axons and clinical and neuropathological features. RESULTS:Virtually all patients showed small amounts of residual CSN axons (0.87%, range 0.02-9.98%), with 50 patients (92.6%) showing less than 2.0% of residual axons. The patients who showed psychological symptoms within the first year of the disease had significantly more residual CSN axons than the remaining patients did (1.50% vs. 0.40%, p < 0.01). Patients with a short disease duration and neocortical-type Lewy body pathology tended to have more preserved CSN axons, although this difference was not statistically significant. Fifty-three patients (98.1%) who had neurofibrillary tangles in the brain and strong concomitant Alzheimer's disease (AD) pathology also had statistically significantly more preserved CSN axons. The patient with the most preserved CSN axons showed different characteristics from the results, except for the first symptom. CONCLUSION:Psychological symptoms within the first year of the disease, a short disease duration, neocortical-type Lewy body pathology, and strong concomitant AD pathology may be related to mild CSN degeneration in DLB patients. Thus, DLB patients with broad LB pathology in the brain in the early stages may show mild CSN degeneration.
摘要
背景: 阐明影响路易体 (DLB) 患者尸检证实的痴呆的心脏交感神经去神经功能的特征。 方法: 54 例经尸检证实的 DLB 患者入组。用抗酪氨酸羟化酶抗体对左心室前壁组织标本进行免疫染色,以鉴定儿茶酚胺能神经轴突。我们将免疫染色区域量化为残余心脏交感神经 (CSN) 轴突,并检查残余 CSN 轴突的程度与临床和神经病理特征之间的关系。 结果: 几乎所有患者都显示少量残留的 CSN 轴突 (0.87%,范围 0.02-9.98%),50 例患者 (92.6%) 显示少于 2.0% 的残留轴突。在疾病第一年内出现心理症状的患者 CSN 轴突残留明显多于其余患者 (1.50% vs. 0.40%,p <0.01)。病程短、新皮层型路易体病理的患者倾向于保留更多的 CSN 轴突,尽管这种差异无统计学意义。53 例 (98.1%) 脑部有神经原纤维缠结和强烈伴随阿尔茨海默病 (AD) 病理的患者也有统计学显著更多的 CSN 轴突保留。CSN 轴突保存最多的患者,除首发症状外,其特征与结果不同。 结论: 疾病第一年内的心理症状、病程短、新皮层型路易体病理、伴发 AD 病理强烈可能与 DLB 患者 CSN 轻度变性有关。因此,早期脑内有广泛 LB 病理的 DLB 患者可能表现为轻度 CSN 变性。
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METHODS:BACKGROUND:Neuroinflammation has been recognized as an important factor in the pathogenesis of Alzheimer's disease (AD). One of the most recognized pathways in mediating neuroinflammation is the prostaglandin E2-EP1 receptor pathway. OBJECTIVE:Here, we examined the efficacy of the selective EP1 antagonist ONO-8713 in limiting amyloid-β (Aβ), lesion volumes, and behavioral indexes in AD mouse models after ischemic stroke. METHODS:Transgenic APP/PS1, 3xTgAD, and wildtype (WT) mice were subjected to permanent distal middle cerebral artery occlusion (pdMCAO) and sham surgeries. Functional outcomes, memory, anatomical outcomes, and Aβ concentrations were assessed 14 days after surgery. RESULTS:pdMCAO resulted in significant deterioration in functional and anatomical outcomes in the transgenic mice compared with the WT mice. No relevant differences were observed in the behavioral tests when comparing the ONO-8713 and vehicle-treated groups. Significantly lower cavitation (p = 0.0373) and percent tissue loss (p = 0.0247) were observed in APP/PS1 + ONO-8713 mice compared with the WT + ONO-8713 mice. However, the percent tissue injury was significantly higher in APP/PS1 + ONO-8713 mice compared with WT + ONO-8713 group (p = 0.0373). Percent tissue loss was also significantly lower in the 3xTgAD + ONO-8713 mice than in the WT + ONO-8713 mice (p = 0.0185). ONO-8713 treatment also attenuated cortical microgliosis in APP/PS1 mice as compared with the vehicle (p = 0.0079); however, no differences were observed in astrogliosis across the groups. Finally, APP/PS1 mice presented characteristic Aβ load in the cortex while 3xTgAD mice exhibited very low Aβ levels. CONCLUSION:In conclusion, under the experimental conditions, EP1 receptor antagonist ONO-8713 showed modest benefits on anatomical outcomes after stroke, mainly in APP/PS1 mice.