大鼠致痫后血清和脑组织皮质醇水平的测定及其意义

应用放免技术测定了马桑内酯致痫和对照组大鼠大脑皮层和海马脑组织皮质醇含量及血清皮质醇水平结果显示，血清对照组为２．７７±２．０７ｎｇ／ｍｌ，致痫组为０．９８±０．７５ｎｇ／ｍｌ，两组比较无显著差异（Ｐ＞０．０５）；海马正常对照组为２５．７７±１２．９８ｎｇ／ｇ湿重，致痫组为０．９８±０．４２ｎｇ／ｇ湿重组织，海马致痫组显著降低（Ｐ＜０．０１）；大脑皮层对照组为８．８３±１．９６ｎｇ／ｇ湿重，致痫组为０．３３±０．１１ｎｇ／ｇ湿重组织，大脑皮层致痫组降低极为显著（（Ｐ＜０．００１）。表明致痫后大鼠大脑皮层、海马脑组织皮质醇含量均明显降低，提示皮质醇在癫痫的发病中起重要作用。     

Education and Levels of Salivary Cortisol Over the Day in US Adults

Background  

Dysregulation of the hypothalamic–pituitary–adrenal axis is hypothesized to be an important pathway linking socioeconomic position and chronic disease.     

脑卒中患者血浆皮质醇变化与意识障碍的关系

用放免法检测５０例脑卒中患者早期和恢复期的血浆皮质醇，结果显示脑出血组和脑梗塞组均比对照组升高（Ｐ〈０．０１，Ｐ〈００５），病情轻，重二组比较皮质醇值有显著差异（Ｐ〈０．０１），康复组与死亡组比较皮质醇有显著差异（Ｐ〈０．０１），提示脑卒中早期皮质醇值升高，其程度与意识障碍和运动障碍有关，其值可作为判断病情和估计预后的指标。     

Increased Cortisol Levels in Aging and Alzheimer's Disease in Postmortem Cerebrospinal Fluid

The hypothalamo-pituitary-adrenal (HPA) axis is activated during aging and even more so in dementia. Increased levels of corticosteroids may be neurotoxic. Therefore we have investigated cortisol levels in cerebrospinal fluid (CSF) of Alzheimer patients and controls. Ventricular postmortem CSF was collected from clinically and neuropathologically well-defined Alzheimer patients (n = 26) and control subjects (n = 21). In the group of Alzheimer patients the mean CSF total cortisol level was 83% higher than that in the controls. In presenile Alzheimer patients (< 65 years of age; n = 13) the CSF-cortisol level was 5 times higher than that of presenile controls (n = 7). In contrast, senile Alzheimer patients (n = 13) and controls of over 65 years of age (n = 14) did not show a significant difference in CSF-cortisol levels. The presence or absence of a difference in the cortisol-CSF levels in, respectively, presenile or senile Alzheimer patients as compared to controls was due to the 3.5-fold rise of CSF-cortisol in control subjects over 65 years of age as compared with controls under 65 years of age. The CSF-cortisol levels in presenile and senile Alzheimer patients were similar. No significant correlation was observed in the Alzheimer patients between age of onset of the dementia and CSF cortisol levels or duration of Alzheimer's disease and CSF cortisol levels. The finding that in senile Alzheimer patients cortisol levels were similar to those of unaffected age-matched controls does not seem to support the cortisol neurotoxicity hypothesis. On the other hand, it should be noted that postmortem ventricular CSF cortisol levels were found to be 13–16 times higher than lumbar puncture CSF cortisol levels of ambulatory patients. This means that the ventricular CSF levels probably reflect the reaction of the HPA-axis to the process of dying rather than the basal levels of this system. The exact consequences of elevated HPA-axis activity for the human brain should be studied in more detail.     

睡眠剥夺对大鼠血清MBP及皮质醇含量的影响

目的　测定大鼠睡眠剥夺 ( sleep deprivation,SD)后血清髓鞘碱性蛋白 ( myelin basic protein,MBP)和皮质醇水平变化 ,观察 SD对大脑的损害情况。方法　采用小平台水环境法建立 SD模型 ,以大平台组 ( TC)和正常笼养组 ( CC)作为对照组 ,采用酶联免疫吸附法测定 MBP水平 ,并用双抗体放射免疫法测定皮质醇水平。观察大鼠经 1、3、5 d SD后上述指标变化。结果　与 CC组比较 ,SD 1、3、5 d后血清皮质醇水平均增高 ,与 TC组比较 ,SD3、5 d血清皮质醇水平增高 ,差异有显著性 ;SD5 d后血清 MBP水平增高 ,SD1、3 d水平差异无显著性。TC组与 CC组比较 ,血清皮质醇水平增高而 MBP水平差异无显著性。结论　长时间 SD可引起脑器质性损害。     

Maternal Cortisol Levels and Behavior Problems in Adolescents and Adults with ASD

Using daily diary methods, mothers of adolescents and adults with ASD (n = 86) were contrasted with a nationally representative comparison group of mothers of similarly-aged unaffected children (n = 171) with respect to the diurnal rhythm of cortisol. Mothers of adolescents and adults with ASD were found to have significantly lower levels of cortisol throughout the day. Within the ASD sample, the son or daughter’s history of behavior problems interacted with daily behavior problems to predict the morning rise of the mother’s cortisol. A history of elevated behavior problems moderated the effect of behavior problems the day before on maternal cortisol level. Implications for interventions for both the mother and the individual with ASD are suggested.     

Conversational Behaviors in Youth with High-functioning ASD and Asperger Syndrome

Twenty-nine youth with autism spectrum disorders and 26 with typical development between 12 and 18 years of age were engaged in structured interviews (ADOS). The interviews were videotaped and rated for atypical conversational behaviors by trained raters, using the Pragmatic Rating Scale (Landa et al. Psychol Med 22:245–254, 1992). The ASD group was divided into AS and HFA/PDD-NOS subgroups. Significant differences were found among groups on approximately one-third of the PRS items. These items involved primarily the management of topics and information, reciprocity, intonation, and gaze management. The only differences to reach significance between the AS and HFA/PDD-NOS group were a greater tendency for overly formal speech on the part of the AS group, and more difficulty with gaze management on the part of the group with HFA/PDD-NOS. The implications of these findings for understanding and treating conversational deficits in ASD are discussed.     

The Effects of Sleep Deprivation on the Circadian Rhythm of Plasma Cortisol Levels in Depressive Patients

The circadian rhythm of plasma cortisol levels was studied in 20 endogenous depressive patients who received one-night sleep deprivation therapy and 10 normal controls who were also deprived of sleep together with patients by estimation at four-hourly intervals over 36 hours. The mean values at each sampling time were compared. The result can be summarized as follows: The mean values of depressive patients tended to be higher than those of controls on the day following sleep deprivation. In depressive patients the mean values on the following day were higher compared to those on the preceding day. In the patients who responded well to sleep deprivation therapy, the circadian variation of mean values which was obscure the preceding day showed an evident rhythm the following day. These findings suggest that sleep deprivation may cause a different effect between depressive patients and normal subjects, and that the possible mechanism of the anti-depressive efficacy of sleep deprivation may be to normalize the disturbed rhythm of the physiological function in depressive patients.     

慢性应激抑制卒中后大鼠海马内源性神经干细胞增殖和分化研究

目的 观察慢性应激对卒中后海马内源性神经干细胞增殖和分化的影响。方法 将雄性SD大鼠分为正常、卒中、慢性应激组。建立左侧大脑中动脉闭塞卒中动物模型并予以慢性不可预见温和应激刺激结合孤养。经溴脱氧尿苷嘧啶（BrdU）标记，免疫组化、荧光双标染色及共聚焦成像动态检测并比较各研究组大鼠左侧海马齿状回BrdU及其与神经元核性蛋白（NeuN）共表达。结果 与卒中组相比，慢性应激组大鼠病灶侧海马齿状回BrdU+细胞数在脑梗死后第7天未见减少，第21天明显减少（28.5±1.9 vs 72.2±1.4），差异有统计学意义（P<0.001）。与卒中组相比，慢性应激组大鼠病灶侧海马齿状回BrdU+/NeuN+细胞比例在脑梗死后30 d[（69.0±3.4）%）]和45 d[（78.3±2.4）%]均明显减少，差异有统计学意义（P<0.001； P<0.01）。结论 慢性应激能明显抑制卒中后海马内源性神经干细胞的增殖和分化，可能是卒中后抑郁发病的因素之一。     

复智散对阿尔茨海默病大鼠海马内源性神经干细胞增殖的影响

目的观察复智散（FZS）对Alzheimer病（AD）模型大鼠海马齿状回内源性神经干细胞增殖的影响。方法采用β淀粉样蛋白25—35（Aβ25—35）侧脑室注射制作AD大鼠模型。采用Morris水迷宫检测大鼠的学习记忆能力,免疫荧光检测大鼠海马5-溴脱氧尿嘧啶（BrdU）阳性细胞表达,免疫组化检测海马增殖细胞核抗原（PCNA）阳性细胞表达,并对海马齿状回下颗粒层、海马门、分子层分别进行BrdU、PCNA阳性细胞计数。结果与模型组比较,健康对照组、假手术组和FZS治疗组大鼠水迷宫实验中的平均逃避潜伏期缩短（P〈0．05）,齿状回颗粒细胞下层BrdU、PCNA阳性细胞数量明显增加（P〈0．05）,但后三组之间比较差异无统计学意义。结论FZS可促进AD模型大鼠海马齿状回内源性神经干细胞增殖。     

Effects of Methylphenidate and Bupropion on DHEA-S and Cortisol Plasma Levels in Attention-deficit Hyperactivity Disorder

We evaluated plasma levels of DHEA-S and cortisol before and after treating ADHD patients with one of two medications: methylphenidate (n = 12) or bupropion (n = 10). Boys with ADHD (combined type) were evaluated with the Korean ADHD rating scale (K-ARS) and the computerized ADHD diagnostic system (ADS). All assessments were measured at baseline and repeated after 12 weeks. There were significant clinical improvements in both treatment groups as measured by K-ARS and ADS. DHEA-S levels increased from baseline to endpoint, but cortisol levels did not change significantly. This study suggests that both methylphenidate and bupropion increase plasma levels of DHEA-S in boys with ADHD.     

Cerebrospinal Fluid Levels of Neuropeptides, Cortisol, and Amino Acids in Patients with Epilepsy

Summary: We measured lumbar cerebrospinal fluid (CSF) levels of somatostatin, cholecystokinin, neurotensin, atrial natriuretic factor, vasoactive inhibitory peptide, neuropeptide Y, adrenocorticotrophic hormone, corticotropin releasing hormone, β-endorphin, metenkephalin, cortisol, alanine, glycine, aspartate, glutamate, taurine, and γ-aminobutyric acid in 25 inpatients with epilepsy at known interictal and postictal times and in 11 neurologically normal volunteers. There were no significant differences between interictal or postictal complex partial seizures (CPS), postictal generalized tonic-clonic seizures (GTC), and control CSF neuropeptide, cortisol, and amino acid (AA) levels. However, there were nonsignificant trends for CSF levels of several neuropeptides to be increased after CPS and GTC as compared with interictal baseline levels. There were significant correlations between levels of certain CSF neuropeptides or (AAs) and serum antiepileptic drug (AED) levels. Several correlations were noted between CSF levels of AAs, including a correlation between the excitatory neurotransmitters aspartate and glutamate identified only after CPS.     

Minocycline对血管性抑郁小鼠抑郁行为及神经递质的作用

目的 探讨minocycline抑制炎症反应对血管性抑郁小鼠行为及神经递质的影响。 方法 成年雄性CD1小鼠随机分为3组,每组各10只,实验组造模后立即腹腔注射minocycline每日1 次连续7 d（30 mg/kg）,对照组造模后给予同等剂量的生理盐水,假手术组除不阻断颈动脉供 血外,其余手术操作与实验组相同,术后同样给予腹腔注射相应剂量的生理盐水。术后第8天起 行悬尾实验（第8天）、旷场实验（第9天）检测抑郁行为,水迷宫定向航行实验（第10天）检测认 知能力。术后第11天处死取脑,分离海马匀浆,酶联免疫吸附测定（enzyme-linked immunosorbent assay,ELISA）试剂盒检测肿瘤坏死因子-α（tumor necrosis factor α,TNF-α）、白细胞介素-1β （interleukin-1β,IL-1β）及白细胞介素-6（interleukin-6,IL-6）含量,并通过高效液相色谱法（high performance liquid chromatography,HPLC）对抑郁相关的单胺类神经递质进行检测,包括5-羟色胺 （5-hydroxytryptamine,5-HT）、去甲肾上腺素（norepinephrine,NE）及多巴胺（dopamine,DA）。 结果 3组小鼠悬尾实验不动时间差异有显著性［实验组：（174.7 5±11.37）s,对照组： （194.32±14.32）s,假手术组：（169.62±19.27）s,F =6.59,P =0.005］;与对照组相比,实验组和假手 术组悬尾不动时间显著缩短;3组小鼠探洞次数、活动时间、活动路程差异显著（F =6.17,P =0.008; F =11.55,P＜0.001;F =13.47,P＜0.001）;与对照组相比,实验组与假手术组探洞次数明显增多［实 验组：（50.86±9.23）次,对照组：（35.73±11.96）次,假手术组：（48.14±10.16）次］,活动时 间与活动总路程均明显延长［实验组：（786.70±27.51）s,对照组：（738.88±36.00）s,假手术组： （807.90±33.16）s;实验组：（37 171.42±8493.40）mm,对照组：（28 992.91±5760.03）mm,假手术 组：（47 206.23±8219.84）mm］;水迷宫实验潜伏期差异有显著性［实验组：（87.38±13.36）s,对照 组：（88.50±19.88）s,假手术组：（44.38±19.76）s,F =16.09,P＜0.001］,与假手术组相比,实验组 和对照组潜伏期显著延长。炎症因子检测提示,3组海马TNF-α、IL-1β及IL-6差异具有显著性［实 验组：（141.10±24.36）pg/100 mg,对照组：（167.6±15.91）pg/100 mg,假手术组：（123.8±15.53） pg/100 mg,F =13.42,P＜0.001;实验组：（5.32±1.89）pg/mg,对照组：（10.31±2.83）pg/mg,假手术组： （4.50±2.07）pg/mg,F =18.69,P＜0.001;实验组：（20.01±3.62）pg/mg,对照组：（24.39±5.04）pg/mg, 假手术组：（18.40±3.78）pg/mg,F =5.49,P =0.010］;与对照组相比,实验组与假手术组3种炎性 细胞因子均显著降低。3组海马5-HT及DA含量差异有显著［实验组：（3.89±1.21）ng/ml,对照组： （3.13±1.44）ng/ml,假手术组：（5.01±1.68）ng/ml,F =4.17,P =0.026;实验组：（10.72±2.65）ng/ml, 对照组：（7.99±2.31）ng/ml,假手术组：（11.76±3.10）ng/ml,F =5.18,P =0.012］;与对照组相 比,实验组和假手术组DA含量显著增加,实验组5-HT含量差异无显著性,而假手术组5-HT含量增 多;3组NE含量差异无显著性［实验组：（3.97±1.35）ng/ml,对照组：（3.16±1.55）ng/ml,假手术组： （4.68±1.99）ng/ml,F =2.13,P =0.139］。 结论 Minocycline能够抑制血管性抑郁小鼠炎症因子的表达,抗炎症治疗可改善其抑郁行为,对认 知损害未观察到明显改善,相关的神经递质以DA的改变为最明显。