阿尔茨海默病(AD)患者嗅觉障碍的研究分析

目的探索阿尔茨海默病(AD)患者的嗅球体积和嗅沟深度与健康人体的差异性,同时分析AD与嗅觉障碍之间的关系。方法选取我院在2014年3月至2015年7月收取的41例AD患者作为主体研究对象,同时选取我院体检中心正常人群40例作为对照研究对象,对两组患者的嗅觉功能进行测试,并对比其嗅沟深度、嗅球体积。结果 AD组41例中嗅觉正常有11例(26.8%),健康组40例中嗅觉正常有30例(75.0%),两组正常嗅觉对比有统计学意义(P<0.01);AD组嗅球体积平均值为(36.50±3.98)mm3,健康组为(46.59±6.22)mm~3,两组平均值对比具有统计学意义(P<0.05);AD组嗅沟深度平均值为(7.60±1.49)mm,健康组为(7.63±1.54)mm,两组平均值对比不具有统计学意义(P>0.05)。结论阿尔茨海默病患者出现嗅觉障碍时其嗅沟深度不会发生,嗅球体积会减小,而嗅觉障碍的检测可以作为阿尔茨海默病患者早期诊断的参考指标。     

嗅球注射甲苯对小鼠嗅觉辨识记忆和嗅球5-羟色胺能神经元的影响

目的观察嗅球注射甲苯对嗅觉功能、嗅球形态及嗅球神经生化的影响。方法甲苯1.0和3.0μL分别注入小鼠的嗅球,术后d3,5,7和14进行嗅觉辨识行为测试;术后d14免疫组织化学检测嗅球细胞5-羟色胺(5-HT)含量和5-HT能神经元数量;HE染色,显微镜下进行嗅球形态学观察。结果嗅球注射甲苯引起小鼠嗅觉记忆明显减弱甚至缺失,大剂量时难以逆转;嗅球内5-HT免疫反应阳性细胞减少;显微镜下见嗅球明显病理改变。结论甲苯对嗅觉功能产生抑制作用,嗅球细胞变性及嗅球5-HT明显减少是其原因之一。     

显微镜下与内镜下经鼻-蝶窦手术对垂体瘤患者术后嗅觉功能的影响

目的 探讨显微镜与内镜两种手术方式对垂体瘤患者术后嗅觉功能的影响.方法 选取垂体瘤患者进行非随机对照研究.采用中国科学院半导体研究所研制的五味试嗅液对入组患者术前、术后1周和术后1个月的嗅觉功能进行评估.结果 共收治45例符合研究条件的垂体瘤患者,最终31例患者纳入分析,其中内镜下经鼻-蝶窦手术组(Ⅰ组)15例;显微镜下经鼻-蝶窦手术组(Ⅱ组)16例.术前两组患者对每种嗅素的嗅觉识别阈差异无统计学意义(P=0.82).与术前相比,两组患者术后1周均出现嗅觉功能减退甚至消失,平均嗅觉识别阈分别为(4.59 ±0.32)和(4.59±0.31) (P =0.99).两组患者术后1个月平均嗅觉识别阈分别为(3.19±0.40)和(2.76±0.36) (P =0.003),并且显微镜组患者嗅觉异常率明显低于内镜组,分别为6.25％和40.00％,差异有统计学意义(P=0.04).结论 在显微镜下与内镜下经鼻-蝶窦切除垂体瘤,都对患者的主观嗅觉功能产生短期影响,在术后早期嗅觉功能恢复方面,显微镜下操作可能更优于内镜操作.     

慢性鼻 -鼻窦炎伴鼻息肉病人鼻内镜手术围手术期处理对嗅功能的影响

目的 研究慢性鼻-鼻窦炎(chronic rhinosinusitis,CRS)伴鼻息肉病人鼻内镜手术(endoscopic sinus surgery,ESS)围手术期处理对嗅功能的影响.方法 选取2017年1月至2019年2月青岛大学附属青岛市市立医院行ESS治疗的CRS伴有鼻息肉及嗅觉障碍病人122例,采用随机数字表法分为四组,ESS围手术期给予不同方式处理,A组术后给予甲泼尼龙联合银杏叶提取物治疗(n=31);B组术后给予纳吸棉联合布地奈德混悬液填塞鼻腔治疗(n=31);C组术后给予甲泼尼龙治疗(n=30);D组术后给予布地奈德喷鼻剂喷鼻治疗(n=30).所有病人于术前、术后1个月、术后3个月行T&T嗅觉检测.结果 四组嗅觉评分术前[A组4.2(3.8,4.6)分,B组4.2(3.8,4.6)分,C组4.0(3.6,4.4)分,D组4.2(3.8,4.65)分]、术后1个月[A组3.6(3.2,4.0)分,B组3.0(2.6,3.6)分,C组3.5(3.2,4.0)分,D组3.4(3.2,4.0)分]、术后3个月[A组3.2(2.8,3.6)分,B组2.6(2.2,2.8)分,C组3.2(2.75,3.6)分,D组3.2(2.6,3.65)分]比较,差异有统计学意义(P<0.05);术后1个月、3个月A、C、D组评分结果组间比较差异无统计学意义(P>0.05);B组术后1个月、3个月评分结果低于其他三组,差异有统计学意义(P<0.05);B组术后3个月总改善率为83.9％,高于其他三组,差异有统计学意义(P<0.05).结论 CRS伴鼻息肉病人行ESS及术后辅以糖皮质激素治疗可以提高自身嗅觉功能,术后纳吸棉联合布地奈德混悬液填塞鼻腔对嗅觉功能改善最为显著.     

CT与核磁共振在腔隙性脑梗死中的临床诊断价值对比分析

目的:研究CT与核磁共振在腔隙性脑梗死中的临床诊断价值。方法:选择我院于2017年2月至2018年2月收治的98例腔隙性脑梗死患者进行回顾性分析,两种患者分为观察组(采用核磁共振成像MRI检查)和对照组(采用CT检查),每组46例,研究患者的CT和核磁共振诊断结果,分析两种诊断方式的临床价值。结果:观察组患者MRI检查出的病灶个数明显98个多于对照组CT检查出的病灶个68个,P0.05,产生统计学意义。观察组患者检查出现来的病灶体积大小小于对照组组患者CT检查病灶的体积大小,差异显著,P0.05,产生统计学意义。观察组确诊为梗死的有46例,阳性率为100%,对照组确诊为37例,阳性率为80.43%,P0.05,产生统计学意义。结论:MRI检查诊断在腔隙性脑梗死疾病的诊断中具有较高的诊断准确率,可以检查出患者体内的微小病灶,可以临床推广使用。     

鼻内镜手术对鼻窦炎伴鼻息肉患者嗅觉功能的影响

目的研究鼻内镜手术对鼻窦炎伴鼻息肉患者嗅觉功能的影响。方法98例鼻窦炎伴鼻息肉患者,随机分为观察组和对照组,每组49例。对照组患者实施常规摘除手术进行治疗,观察组患者实施鼻内镜手术进行治疗。比较两组患者治疗效果、并发症发生情况及治疗前后鼻气道总阻力、嗅觉功能评分。结果观察组患者的治疗总有效率为100.00%,明显高于对照组的81.63%,差异具有统计学意义(χ^2=9.9101,P=0.0016<0.05)。手术前,两组患者的鼻气道总阻力和嗅觉功能评分比较差异均无统计学意义(P>0.05);手术后,两组患者的鼻气道总阻力和嗅觉功能评分均较手术前明显改善,且观察组改善效果优于对照组,差异具有统计学意义(P<0.05)。观察组并发症发生率6.12%明显低于对照组的26.53%,差异具有统计学意义(χ^2=7.4695,P=0.0063<0.05)。结论临床在对鼻窦炎伴鼻息肉患者通过鼻内镜手术方案治疗能提高治疗效果,具有良好的安全性,对改善患者的鼻气道总阻力和嗅觉功能发挥了重要作用,是理想的手术方案。     

嗅觉、听觉功能的检查对轻度认知功能障碍早期诊断的价值

目的 探讨嗅觉、听觉功能检查运用于轻度认知功能障碍中的诊断价值.方法 选择轻度认知功能障碍患者90例作为观察组,另选择同一时间纳入的40例健康体检者作为对照组,分别实施嗅觉及听觉功能的检查,比较两组检查结果.结果 观察组的嗅觉察觉阈与识别阈均高出对照组(P＜0.05);观察组平均听力轻度、中度及重度损失的发生率均高于对...     

迷迭香精油通过嗅觉通路改善小鼠学习记忆的研究

目的探讨迷迭香精油通过嗅觉通路改善C57BL/6小鼠学习记忆能力及其可能的机制。方法通过鼻吸入迷迭香精油的方法 ,以毁损嗅上皮模型作对照,分组进行Lashley-III水迷宫和嗅觉辨识记忆实验,并进行免疫组化,观察各组小鼠海马CA1区乙酰胆碱酯酶、谷氨酸的表达情况。结果迷迭香精油组小鼠的水迷宫实验和嗅觉辨别记忆实验潜伏期低于其他组(P<0.05),免疫组化结果显示该组小鼠海马CA1区乙酰胆碱酯酶、谷氨酸的表达增强。结论迷迭香精油能够通过嗅觉通路改善小鼠的学习记忆功能,其机制可能与嗅觉通路中神经递质的改变有关。     

补骨脂素对绝经后大鼠骨质疏松及PI3K/Akt/mTOR信号通路的影响

目的:研究补骨脂素对绝经后大鼠骨质疏松及磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的影响。方法:将60只健康雌性SD大鼠随机分为正常组、模型组、阳性对照组(0.09 mg/kg雌二醇)和补骨脂素低、中、高剂量组(22、44、88 mg/kg),每组10只。除正常组外,其余各组大鼠均采用卵巢摘除去势法建立绝经后骨质疏松模型。术后正常饲养2个月,正常组和模型组大鼠灌胃等体积生理盐水,各药物组大鼠灌胃相应药液;灌胃体积均为0.005 mL/g,每天1次,连续98天。末次给药24 h后,测定大鼠右侧下肢股骨和椎骨的骨密度,血清中钙离子、骨钙素、Ⅰ型前胶原N端前肽(P1NP)含量和骨形态发生蛋白2(BMP2)、血管内皮生长因子(VEGF)水平,以及股骨组织中PI3K、Akt、mTOR mRNA及蛋白的表达水平。结果:与正常组比较,模型组大鼠股骨和椎骨的骨密度以及血清中钙离子、骨钙素、P1NP含量和BMP2、VEGF水平均显著降低,PI3K、Akt、mTOR mRNA及蛋白的表达水平均显著升高(P<0.05或P<0.01)。与模型组比较,补骨脂素中、高剂量组和阳性对照组大鼠股骨和椎骨的骨密度以及血清中钙离子、骨钙素、P1NP含量和BMP2(补骨脂素中剂量组除外)、VEGF(补骨脂素中剂量组除外)水平均显著升高,各药物组PI3K、Akt、m TOR mRNA(补骨脂素低剂量组除外)及蛋白表达水平均显著降低(P<0.05或P<0.01),且高剂量组股骨骨密度和钙离子、BMP2水平以及PI3K蛋白表达水平均显著高于阳性对照组(P<0.05),mTOR mRNA表达水平显著低于阳性对照组(P<0.05)。结论:补骨脂素可改善绝经后大鼠的骨质疏松,其机制可能与抑制PI3K/Akt/mTOR信号通路有关。     

警惕嗅觉失灵

嗅觉,是人体五大外部感觉之一(其他4个为视觉、听觉、触觉和味觉)。人的嗅觉可辨别成千上万种气味,但也会受到如温度、年龄、环境等很多因素的影响:温度低嗅觉灵敏度较高,所以人在冬季比夏季嗅觉要灵敏些;年轻人的嗅觉比老年人的嗅觉灵敏;如果长时间接触某一种气味,就会形成嗅觉的适应性,正所谓"入芝兰之室,久而不闻其香;入鲍鱼之肆,久而不闻其臭"。     

Drug Targeting to the Brain: Transfer of Picolinic Acid Along the Olfactory Pathways

Picolinic acid (PA) protects against quinolinic acid- and kainic acid-induced neurotoxicity in the brain. To study the uptake of PA to the brain, we administered [3 H]PA via a unilateral nasal instillation or iv injection to mice. Autoradiography demonstrated a rapid uptake of radioactivity in the olfactory nerve layer and in the ipsilateral olfactory bulb (OB) following nasal instillation of [3 H]PA. After 4 h, there was a high level of radioactivity in the central parts of the ipsilateral OB and olfactory peduncle. Moreover, iv injection of [3 H]PA demonstrated a selective uptake and retention of radioactivity in the OB. Gas chromatography-mass spectrometry (GC-MS) demonstrated the presence of PA and PA-glycine conjugate in the OB. In mice with reduced peripheral olfactory innervations there was a decreased uptake of [3 H]PA in the OB as compared to controls suggesting that an intact olfactory neuroepithelium is a prerequisite for an uptake of PA to the OB. There is an increased interest in brain targeting of drugs with limited ability to pass the blood-brain barrier. The present results demonstrate that PA fulfils structural requirements for a transfer along the olfactory pathways to the brain.     

大鼠嗅球切除抑郁症动物模型的改进与评价

目的改进大鼠嗅球切除(olfactory bulbectomy,OB)抑郁症动物模型的建立方法并评价模型的可行性。方法应用探针捣毁嗅球与负压吸引相结合的方法进行嗅球切除,恢复2周后分组:假手术组、嗅球切除模型组、氟西汀(10 mg.kg-1,ig,每天1次,14 d)治疗组。给药2周后通过开场实验、蔗糖饮水实验和逃避实验检测各组大鼠的行为学。结果与假手术组比较,嗅球切除模型组大鼠开场实验水平运动得分和垂直运动得分明显增多,蔗糖偏嗜度明显降低,逃避失败次数明显增多,长期氟西汀治疗能够逆转嗅球切除引起的行为学改变。结论大鼠嗅球切除后出现抑郁样行为学改变,经典抗抑郁药物治疗有效,通过改进建立了稳定的大鼠嗅球切除抑郁症动物模型及可靠的评价方法。     

Olfactory Bulb D2/D3 Receptor Availability after Intrastriatal Botulinum Neurotoxin-A Injection in a Unilateral 6-OHDA Rat Model of Parkinson’s Disease

Olfactory deficits occur as early non-motor symptoms of idiopathic Parkinson’s disease (PD) in humans. The first central relay of the olfactory pathway, the olfactory bulb (OB), depends, among other things, on an intact, functional crosstalk between dopaminergic interneurons and dopamine receptors (D₂/D₃R). In rats, hemiparkinsonism (hemi-PD) can be induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB), disrupting dopaminergic neurons of the substantia nigra pars compacta (SNpc). In a previous study, we showed that subsequent injection of botulinum neurotoxin-A (BoNT-A) into the striatum can reverse most of the pathological motor symptoms and normalize the D₂/D₃R availability. To determine whether this rat model is suitable to explain olfactory deficits that occur in humans with PD, we examined the availability of D₂/D₃R by longitudinal [¹⁸F]fallypride-PET/CT, the density of tyrosine hydroxylase immunoreactivity in the OB, olfactory performance by an orienting odor identification test adapted for rats, and a connectome analysis. PET/CT and immunohistochemical data remained largely unchanged after 6-OHDA lesion in experimental animals, suggesting that outcomes of the 6-OHDA hemi-PD rat model do not completely explain olfactory deficits in humans. However, after subsequent ipsilateral BoNT-A injection into the striatum, a significant 8.5% increase of the D₂/D₃R availability in the ipsilateral OB and concomitant improvement of olfactory performance were detectable. Based on tract-tracing meta-analysis, we speculate that this may be due to indirect connections between the striatum and the OB.     

Distribution of nimodipine in brain following intranasal administration in rats

AIM: To determine whether nasally applied nimodipine (NM) could improve its systemic bioavailability and be transported directly from the nasal cavity to the brain. METHODS: NM was administered nasally, intravenously (iv), and orally to male Sprague-Dawley rats. At different times post dose, blood, cerebrospinal fluid (CSF), and brain tissue samples were collected, and the concentrations of NM in the samples were analyzed byHPLC. RESULTS: Oral systemic bioavailability of NM in…     

Visualization of In Vivo Olfactory Uptake and Transfer Using Fluorescein Dextran

Nasal administration of a 3 kDa fluorescein dextran (FD3) solution to rats resulted in transcellular absorption across the olfactory epithelium and transfer to the olfactory bulb within 15 min. After entering the lamina propria, FD3 was transferred in the connective tissue surrounding the olfactory nerve bundles to the olfactory bulb of the brain. More FD3 was absorbed across the olfactory epithelium than across the respiratory epithelium and to the nasal associated lymphoid tissue. Further, the amount of FD3 crossing the olfactory epithelium was region-dependent, with higher amounts absorbed in the turbinates than in the nasal septum. Plastic embedding and sectioning followed by fluorescence microscopy, enabled simultaneous visualization of FD3 in the mucosa and olfactory bulb, as well as the opportunity to store the tissue blocks for a prolonged period of time.     

Drug targeting to the brain: transfer of picolinic acid along the olfactory pathways

Picolinic acid (PA) protects against quinolinic acid- and kainic acid-induced neurotoxicity in the brain. To study the uptake of PA to the brain, we administered [3H]PA via a unilateral nasal instillation or iv injection to mice. Autoradiography demonstrated a rapid uptake of radioactivity in the olfactory nerve layer and in the ipsilateral olfactory bulb (OB) following nasal instillation of [3H]PA. After 4 h, there was a high level of radioactivity in the central parts of the ipsilateral OB and olfactory peduncle. Moreover, iv injection of [3H]PA demonstrated a selective uptake and retention of radioactivity in the OB. Gas chromatography-mass spectrometry (GC-MS) demonstrated the presence of PA and PA-glycine conjugate in the OB. In mice with reduced peripheral olfactory innervations there was a decreased uptake of [3H]PA in the OB as compared to controls suggesting that an intact olfactory neuroepithelium is a prerequisite for an uptake of PA to the OB. There is an increased interest in brain targeting of drugs with limited ability to pass the blood-brain barrier. The present results demonstrate that PA fulfils structural requirements for a transfer along the olfactory pathways to the brain.     

Orbitofrontal cortex dysfunction in obsessive-compulsive disorder? II. Olfactory quality discrimination in obsessive-compulsive disorder.

BACKGROUND: Olfactory quality discrimination is a putative marker of orbitofrontal cortex function in mammals. As this portion of the cerebral cortex was repeatedly implicated in the pathophysiology of obsessive-compulsive disorder (OCD) this study was designed in an attempt to quantify this behavioural function in OCD patients. METHODS AND RESULTS: Olfactory quality discrimination was compared in OCD patients and healthy controls. Thirty two subjects participated in the study: 16 (13 women and 3 men) medication free OCD outpatients and 16 sex and age matched healthy controls. Olfactory tests consisted of determination of detection thresholds to isoamyl acetate, and a three way forced choice quality discrimination task, using isoamyl acetate, citral and eugenol as stimuli. No significant differences in sensitivity and performance of the quality discrimination task between the two groups were found. Within the OCD group the more severely affected patients (Y-BOCS>29) performed significantly better than the less severely affected (Y-BOCS<30) patients on the more difficult part of the quality discrimination task. Within this subgroup of patients the correlation between performance on the olfactory task and a previously reported alternation task tended to be negative as compared to a significantly positive correlation in the control group. CONCLUSIONS: It seems that olfactory quality discrimination may prove to be a useful noninvasive marker of prefrontal cortex function in OCD. Furthermore, the organization of functional modules within the orbitofrontal cortex, rather than a simple dysfunction, may prove to characterize OCD.     

成年大鼠嗅球神经干细胞的培养和鉴定

目的建立成年大鼠嗅球神经干细胞分离培养和鉴定方法,探索新的成年神经干细胞种子来源。方法用无血清方法分离培养成年大鼠嗅球来源的神经干细胞;用克隆培养、BrdU整合的方法检验培养细胞的干细胞特性;用免疫荧光细胞化学的方法检测BrdU、神经干细胞标记物Nestin和SOX2,分化的细胞标记物Tuj1、GFAP、NG2的表达。结果从成年大鼠嗅球能够分离、培养出具有自我更新、增殖的神经球,构成神经球的细胞呈Nestin和SOX2阳性,它们分化后产生Tuj1阳性的神经元、GFAP阳性的星形胶质细胞、NG2阳性的少突胶质细胞。结论成年大鼠嗅球存在神经干细胞,能够在体外进行培养、增殖、分化,是神经干细胞的新的种子来源。     

Transfer of Some Carboxylic Acids in the Olfactory System Following Intranasal Administration

Abstract

The uptake of [¹⁴C]benzoic acid, 4-chloro[¹⁴C]benzoic acid, [³H]phthalic acid and [¹⁴C]salicylic acid in the nasal passages and brain was determined following a unilateral intranasal instillation in mice. An uptake of radioactivity from the nasal mucosa to the ipsilateral olfactory bulb was observed up to 4 h after administration following intranasal instillation of these carboxylic acids whereas the level was low in the contralateral olfactory bulb. Autoradiography of mice given [¹⁴C]benzoic acid and [¹⁴C]salicylic acid by intranasal instillation showed a preferential localization of radioactivity in the axonal and glomerular layer of the olfactory bulb 1 h after the administration. Four hours after administration the radioactivity was present as a gradient from the axonal layer towards the center of the olfactory bulb. Pretreatment of mice with a compound known to damage the olfactory neuroepithelium resulted in a decreased uptake of [¹⁴C]benzoic acid in the olfactory bulb. Thin layer chromatography of supernatants from the ipsilateral olfactory bulbs of mice given [¹⁴C]benzoic acid by nasal instillation indicated that the radioactivity in the bulbs represented unchanged compound. These results suggest that there is a transfer of some aromatic carboxylic acids in the olfactory pathways.