可逆性后部脑病综合征发病机制进展及影像学表现

可逆性后部脑病综合征是一种与多种致病因素相关的临床影像学综合征,以头痛、癫痫发作、精神症状、视觉障碍、意识障碍为主要临床表现,影像学以顶枕叶可逆性脑白质病变为主。该病如果能够得到及时的诊断与治疗,大部分患者的临床症状及影像学改变可以消失;如果不能得到及时正确的诊疗,可能会发生一些不可逆的损伤,严重时甚至危及生命,因此加强对本病的认识、诊断及治疗至关重要。目前该病的发病机制尚不明确,现对其发病机制进展及影像学表现进行综述,以提高临床医师对该病的病理生理机制的认识及提高诊断水平。     

Effect of Bilirubin on the Membrane Potential of Rat Brain Synaptosomes

The effect of the neurotoxic pigment bilirubin on the membrane potential of rat brain synaptosomes was studied by using the tetraphenylphosphonium ion (TTP+) technique. Bilirubin induces a rapid depolarization of synaptosomes, as reflected by an efflux of previously accumulated [3H]TTP+. This phenomenon persisted when the membrane potential across either the plasma membrane of the synaptosome or the inner membrane of the entrapped mitochondria was selectively depressed, thus indicating that both components of the synaptosomal membrane potential were affected by bilirubin. Bovine serum albumin, used at a albumin/bilirubin molar ratio of 1:1, had the capacity to completely prevent and reverse the effect of bilirubin. This fact demonstrates that the bilirubin-induced TPP+ release from synaptosomes is a reversible process that requires the presence of bilirubin interacting with the synaptosomal membranes. These results, together with the inhibition by bilirubin of [3H]TPP+ and [2-14C]acetate uptake by synaptosomal plasma membrane vesicles isolated from rat brain, suggest that bilirubin depresses the membrane potential across the synaptosomal plasma membrane by a mechanism involving alterations in ion permeability. This effect could be of relevance in the pathogenesis of bilirubin encephalopathy.     

Releases of Norepinephrine and Dopamine in Ventriculocisternal Perfusions in Hepatectomized and Laparotomized Rats

Abstract: The completely hepatectomized rat has frequently been used as a model to study changes in the economy of norepinephrine (NE) and dopamine (DA) in hepatic coma. Hypothermia characteristically develops in hepatectomized rats and also occurs in patients in hepatic coma and is associated with improved survival in both. The aims of the present study were to measure both release and uptake of NE and release of DA in brain in warm (37°C) and cool (30–32°C) rats at 3–5 h after laparotomy or hepatectomy. Ventriculocisternal perfusions of the brain were performed on rats under basal conditions and during releases evoked by 40 m M K⁺. Basal releases of NE and DA and evoked release of DA were greater in the warm hepatectomized rats than in all other groups. In some studies, 10⁻⁵ M amitriptyline was added to the perfusates to assess whether neuronal uptake was changed after hepatectomy. Uptake of released NE was equally robust in cool hepatectomized as in cool laparotomized rats but could not be measured in warm hepatectomized rats because of amitriptyline toxicity in these rats. Decreases in NE and increases in DA content were found in most areas of the brain after perfusion. Increased releases of NE and DA may contribute to the pathogenesis of hepatic encephalopathy.     

血S100B蛋白和尿乳酸/肌酐比值对门静脉高压症术后肝性脑病发生的早期预测价值

目的评价血S100B蛋白和尿乳酸/肌酐对乙肝肝硬化门脉高压症术后肝性脑病发生的早期预测价值。方法回顾性分析65例乙肝肝硬化门脉高压症患者的临床资料,动态检测术后24、48和72h的血S100B蛋白和尿乳酸/肌酐比值水平,根据是否发生术后肝性脑病将受试者分为肝性脑病组与非肝性脑病组,并对肝性脑病组患者进行临床分度。结果乙肝肝硬化门脉高压症患者术后发生肝性脑病组72h内血S100B蛋白含量和24 h内尿乳酸/肌酐比值水平明显高于非肝性脑病组(P<0.001);72h内血S100B蛋白含量和24 h内尿乳酸/肌酐比值之间及与肝性脑病的临床分度呈正相关(P<0.001);当血S100B水平在28ng/L,尿乳酸/肌酐比值在0.47时,单独检测72h血S100B蛋白的敏感度、特异度分别为91.2%、93.6%;尿乳酸/肌酐比值预测肝性脑病的敏感度和特异性度以术后24h最高,分别为89.3%和91.7%;如检测72h血S100B蛋白的同时监测术后24h尿乳酸/肌酐比值可显著提高肝性脑病诊断的准确性,联合应用两项指标进行检测,诊断的敏感度和特异度分别为95.7%和98.6%,较两种方法单独应用敏感度和特异度均提高。结论对门静脉高压症患者术后以临床表现为基础,同时监测72h内血S100B蛋白和24h尿乳酸/肌酐比值,对提高术后肝性脑病的早期诊断和临床分度具有一定应用价值。     

新生儿缺氧缺血性脑病血清S-100B蛋白与NBNA评分动态监测 的临床研究

目的:观察新生儿缺氧缺血性脑病(hypoxic-ischemicencephalopathy,HIE)血清S-100B蛋白的动态变化规律,探讨其在HIE早期诊断中的价值,以及其浓度变化与病情严重程度及预后的关系。同时研究围产期高危因素以及NBNA评分在HIE发生发展与预后中的作用。方法:30例住院正常新生儿作为对照组,于出生后采血,55例HIE患儿(HIE组)分别于出生后1天、2天、7天采血,采用酶联免疫吸附试验、双抗体夹心法检测。收集并分析两组围产期相关资料。HIE组并于采血同时进行NBNA评分。结果:(1)HIE患儿生后第一天与第二天血清S-100B蛋白浓度明显高于对照组(P<0.05),生后第七天轻度HIE与对照组比较没有统计意义,中、重度HIE与对照组比较有统计学意义。(2)生后第一天与第二天不同病情组HIE患儿NBNA评分相互比较差异具有统计学意义(P<0.05),第七天轻、中和重度患儿NBNA评分<35分的患儿分别占33.3%,47.1%,100%。结论:动态监测HIE患儿血清S-100B蛋白浓度和NBNA评分的变化,对HIE的早期诊断,严重程度的判断以及预后的估计有重要意义。     

Quercetin protects against diabetic encephalopathy via SIRT1/NLRP3 pathway in db/db mice

Epidemiological studies have found that diabetes and cognitive dysfunction are closely related. Quercetin has been certified with the effect on improving diabetes mellitus (DM) and cognitive impairment. However, the effect and related mechanism of quercetin on diabetic encephalopathy (DE) are still ambiguous. In this study, we used the db/db mice (diabetic model) to discover whether quercetin could improve DE through the Sirtuin1/NLRP3 (NOD-, LRR- and pyrin domain-containing 3) pathway. Behavioural results (Morris water maze and new object recognition tests) showed that quercetin (70 mg/kg) improved the learning and memory. Furthermore, quercetin alleviated insulin resistance and the level of fasting blood glucose. Besides, Western blot analysis also showed that quercetin increased the protein expressions of nerve- and synapse-related protein, including postsynapticdensity 93 (PSD93), postsynapticdensity 95 (PSD95), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of db/db mice. Quercetin also increased the protein expression of SIRT1 and decreased the expression of NLRP3 inflammation-related proteins, including NLRP3, the adaptor protein ASC and cleaved Caspase-1, the pro-inflammatory cytokines IL-1β and IL-18. In conclusion, the present results indicate that the SIRT1/NLRP3 pathway may be a crucial mechanism for the neuroprotective effect of quercetin against DE.     

Sestrin 2 attenuates sepsis‐associated encephalopathy through the promotion of autophagy in hippocampal neurons

Sepsis‐associated encephalopathy (SAE) has typically been associated with a poor prognosis. Although sestrin 2 (SESN2) plays a crucial role in metabolic regulation and the stress response, its expression and functional roles in SAE are still unclear. In the present study, SAE was established in mice through caecal ligation and puncture (CLP). The adeno‐associated virus 2 (AAV2)‐mediated SESN2 expression (ie overexpression and knockdown) system was injected into the hippocampi of mice with SAE, and subsequently followed by electron microscopic analysis, the Morris water maze task and pathological examination. Our results demonstrated an increase of SESN2 in the hippocampal neurons of mice with SAE, 2‐16 hours following CLP. AAV2‐mediated ectopic expression of SESN2 attenuated brain damage and loss of learning and memory functions in mice with SAE, and these effects were associated with lower pro‐inflammatory cytokines in the hippocampus. Mechanistically, SESN2 promoted unc‐51‐like kinase 1 (ULK1)‐dependent autophagy in hippocampal neurons through the activation of the AMPK/mTOR signalling pathway. Finally, AMPK inhibition by SBI‐0206965 blocked SESN2‐mediated attenuation of SAE in mice. In conclusion, our findings demonstrated that SESN2 might be a novel pharmacological intervention strategy for SAE treatment through promotion of ULK1‐dependent autophagy in hippocampal neurons.     

乳果糖联合双歧杆菌三联活菌胶囊在轻微性肝性脑病患者中的应用效果

目的探讨乳果糖联合双歧杆菌三联活菌胶囊在轻微性肝性脑病(MHE)患者中的应用效果。方法选择2015年1月至2019年4月在我院消化科住院就诊的94例MHE患者为研究对象,随机分为观察组和对照组各47例。两组患者均予基础治疗。观察组患者在基础治疗上加用双歧杆菌三联活菌胶囊(630 mg/次,2次/d,温开水送服)联合乳果糖口服液(20 mL/次,3次/d,口服)治疗,连用8周。对照组患者单用乳果糖口服液治疗,剂量、用法及疗程同观察组。观察两组患者治疗前后血氨、血清内毒素(ET)、数字连接试验(NCT)时间和数字符号实验(DST)评分及肠道菌群数量的变化,并比较肝性脑病(HE)的转变率。结果治疗8周后,两组患者血氨、ET和NCT时间均较治疗前明显下降,DST评分较治疗前明显上升,且观察组变化幅度大于对照组(均P0.05)。治疗8周后,两组患者肠道双歧杆菌和乳杆菌数量较治疗前显著增加,大肠埃希菌数量较治疗前显著减少,且观察组变化幅度大于对照组(均P0.05)。治疗后观察组患者HE的转变率为8.51%(4/47),明显低于对照组的23.40%(11/47),差异有统计学意义(χ~2=3.89,P=0.049)。结论乳果糖联合双歧杆菌三联活菌胶囊能显著改善MHE患者智力测验结果,降低HE转化率,其作用机制可能与其能纠正患者肠道菌群紊乱,降低血氨水平,控制内毒素血症相关。