Pathogenesis of HIV-associated dementia and its potential drug targets

HIV-associated dementia (HAD) is a serious complication of AIDS patients. With the wide application of highly active antiretroviral therapy (HAART), the replication of HIV is under effective control and the incidence of HAD is also declined. However, a relatively mild HIV-associated symptom of dementia, called minor cognitively motor disorder (MCMD), become the problem and can not be neglected in the treatment of AIDS. The neural injury caused by HIV may be mediated mainly by macrophages, microglia and astrocytes, though we can not rule out the direct damage on neurons by HIV proteins. To date, the precise mechanism of neural damage caused by HIV remains unclear. The present review tries to figure out the recent progress of pathogenesis and potential drug targets for HAD.     

针刺疗法治疗血管性痴呆的临床研究进展

血管性痴呆（vascular dementia,VD）是由各种脑血管病引起脑组织损害而产生的痴呆,它是仅次于阿尔茨海默病的常见痴呆类型。针刺疗法对血管性痴呆的认知功能及社会活动功能康复有积极作用,临床应用广泛。本文综述中文数据库中近五年相关针刺疗法治疗血管性痴呆临床文献报道,科学评价针刺疗法的优势和不足,以期为临床治疗血管性痴呆提供参考。     

Effects of taurine-zinc on learning and memory abilities of vascular dementia mice

AIM:To observe the effects of taurine-zinc (TZC) on the learning and memory abilities of vascular dementia (VD) mice and to investigate the related mechanism. METHODS:The mice were randomly divided into model group, sham group, and TZC at 50 mg/kg, 100 mg/kg and 200 mg/kg groups. The mice in drug groups were given TZC by gavage at 10 mL/kg once daily. The mice in sham group and model group were given equal volume of distilled water. VD mice were established by intercepting both common carotid arteries and bleeding at caudal vein after 14 d of gavage. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by ELISA. The levels of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) were measured via spectrophotometer. Step-down test and Morris water maze test were used to examine the abilities of learning and memory in the mice. RESULTS:TZC at 50 mg/kg, 100 mg/kg and 200 mg/kg reduced the levels of TNF-α, IL-1β, iNOS and NO in the brain tissues. In the water maze test, TZC at 100 mg/kg and 200 mg/kg significantly decreased the error times and latency compared with model group. In the step-down test, the escape latency was prolonged and error times were lowered significantly by treatment with TZC at 50 mg/kg, 100 mg/kg and 200 mg/kg as compared with model group. CONCLUSION:TZC improves the abilities of learning and memory, which might be related to the reduction of TNF-α, IL-1β, iNOS and NO levels in VD mice.     

MEASUREMENT OF INTERTHALAMIC ADHESION THICKNESS AS A CRITERIA FOR BRAIN ATROPHY IN DOGS WITH AND WITHOUT COGNITIVE DYSFUNCTION (DEMENTIA)

The criteria for brain atrophy in dogs have not yet been established, because of wide variation in the morphology of the ventricles and sulci of the brain depending on the breed and size. In this study, we examined the thickness of the interthalamic adhesion in a transverse magnetic resonance image to investigate normal, to examine the correlation with age, body weight, and breed, and to assess whether measurement would be a useful indicator of brain atrophy. The animals used in this study were of various breeds and weight, and had no identifiable intracranial lesion. They were divided into two groups: a normal group (0.6-15-year-old, n = 66) and a demented aging group (12-18-year-old, n = 12). The interthalamic adhesion thickness in both T1- and T2-weighted transverse images were measured in all dogs. The interthalamic adhesion thickness in the normal and demented groups was 6.79 +/- 0.70 and 3.82 +/- 0.79 mm, respectively. The interthalamic adhesion thickness in the demented group was significantly smaller. In an analysis of the correlation of interthalamic adhesion thickness with age and weight in normal dogs, significant negative and positive correlation was recognized, respectively. However, the strength of these correlations was low. These results suggest that interthalamic adhesion thickness may be a good parameter for evaluating brain atrophy in dogs with cognitive dysfunction.     

基于络脉理论辨治脑小血管病——中医脑病理论与临床实证研究（二）

脑小血管病隐匿起病、缓慢发展、部分可急性发作。根据脑小血管的临床特点,中医病机以脑络荣气虚滞为主。其病机特征是,病位隐曲,责之络脉;内邪杂合,病性复杂;症状广泛,复合证候;病程慢性进展,或有突变加重。系统防治脑小血管病需要全程动态管理,病证系统治疗,最优化治疗,辨病辨证结合,多系统多病同治,复方简药图治,杂合适宜以治。在辛味通络、芳香透络、虫蚁搜络、藤类行络等络病的常用治法基础上,选择使用多汁药物养阴、破血化瘀通络、开窍药物疏通玄府。从络脉荣气虚滞视角探讨脑小血管病,着眼恢复脑窍玄府气化,可以为中医防治脑小血管病的临床决策提供参考。     

滋肾活血方对血管性痴呆大鼠NR2A表达的影响

目的 探讨滋肾活血方对血管性痴呆（vascular dementia,VD）大鼠NR2A表达的影响。方法 采用改良的双侧颈总动脉结扎法（2-VO法）制作VD大鼠模型,将其随机分为假手术组、模型组、滋肾活血组及奥拉西坦组。给药4周后,用免疫组化和RT-PCR检测NR2A及其mRNA的表达。结果 与假手术组相比,模型组NR2A及其mRNA表达均降低（P<0.05）;与模型组相比,滋肾活血组及奥拉西坦组NR2A及其mRNA表达增高（P<0.05）。结论 滋肾活血方可提高VD大鼠的学习记忆能力,这可能与上调NR2A的表达有关。     

Evaluation of interthalamic adhesion size as an indicator of brain atrophy in dogs with and without cognitive dysfunction

Interthalamic adhesion thickness has been previously described as a parameter for quantifying canine brain atrophy and hypothesized to correlate with brain height or ventricular size. However, studies testing this hypothesis are lacking. This retrospective cross‐sectional study aimed to compare interthalamic adhesion thickness, interthalamic adhesion thickness/brain height ratio, and interthalamic adhesion thickness/brain height ratio/lateral ventricle to brain height ratio values in dogs with and without cognitive dysfunction. Medical records for dogs meeting the following inclusion criteria were retrieved from two hospitals: available brain magnetic resonance imaging (MRI) or computed tomography (CT) studies, no cerebral parenchymal lesions, and no prior neurological treatment. For each included dog, values of interthalamic adhesion thickness, interthalamic adhesion thickness/brain height ratio, and interthalamic adhesion thickness/brain height ratio/lateral ventricle to brain height ratio were measured by one observer from transverse CT or MRI images and a consensus was reached. A total of 113 dogs met inclusion criteria. Dogs were divided into three groups based on the following criteria: Young group (no cognitive dysfunction, <9‐year‐old, n = 43), Aging group (no cognitive dysfunction, ≥9‐year‐old, n = 61), and Dementia group (n = 9). All three parameters were significantly lower in the dementia group than in the Young and Aging groups. In the Young and Aging groups, there was significant negative correlation of all three parameters with age and positive correlation of interthalamic adhesion thickness and interthalamic adhesion thickness/brain height ratio/lateral ventricle to brain height ratio with body weight, while there was no correlation of interthalamic adhesion thickness/brain height ratio with body weight (P < 0.05). There were no differences in all three parameters according to skull type or gender. Findings from the current study supported the use of interthalamic adhesion thickness, interthalamic adhesion thickness/brain height ratio, and interthalamic adhesion thickness/brain height ratio/lateral ventricle to brain height ratio for quantifying brain atrophy in dogs with cognitive dysfunction.     

滋肾活血方对血管性痴呆大鼠学习记忆能力和海马形态学的影响

目的 探讨滋肾活血方对血管性痴呆（vascular dementia,VD）大鼠行为学和海马病理形态学的影响。方法 采用改良的双侧颈总动脉结扎法（2-VO法）制作VD大鼠模型,滋肾活血方干预。给药4周后,用水迷宫检测行为学;HE染色观察海马病理形态学的改变。结果 与模型组相比滋肾活血组逃避潜伏期缩短（P<0.05）,跨越平台次数增多（P<0.05）,HE染色示海马损伤明显减轻。结论 滋肾活血方可以改善VD大鼠的学习记忆能力,减轻海马组织损伤,对VD大鼠有一定的治疗作用。