Neuronal protein-tyrosine phosphatase 1B hinders sensory-motor functional recovery and causes affective disorders in two different focal ischemic stroke models

Ischemic brain injury causes neuronal death and inflammation. Inflammation activates protein-tyrosine phosphatase 1B (PTP1B). Here, we tested the significance of PTP1B activation in glutamatergic projection neurons on functional recovery in two models of stroke: by photothrombosis, focal ischemic lesions were induced in the sensorimotor cortex (SM stroke) or in the peri-prefrontal cortex (peri-PFC stroke). Elevated PTP1B expression was detected at 4 days and up to 6 weeks after stroke. While ablation of PTP1B in neurons of neuronal knockout (NKO) mice had no effect on the volume or resorption of ischemic lesions, markedly different effects on functional recovery were observed. SM stroke caused severe sensory and motor deficits (adhesive removal test) in wild type and NKO mice at 4 days, but NKO mice showed drastically improved sensory and motor functional recovery at 8 days. In addition, peri-PFC stroke caused anxiety-like behaviors (elevated plus maze and open field tests), and depression-like behaviors (forced swimming and tail suspension tests) in wild type mice 9 and 28 days after stroke, respectively, with minimal effect on sensory and motor function. Peri-PFC stroke-induced affective disorders were associated with fewer active (FosB⁺) neurons in the PFC and nucleus accumbens but more FosB⁺ neurons in the basolateral amygdala, compared to sham-operated mice. In contrast, mice with neuronal ablation of PTP1B were protected from anxiety-like and depression-like behaviors and showed no change in FosB⁺ neurons after peri-PFC stroke. Taken together, our study identifies neuronal PTP1B as a key component that hinders sensory and motor functional recovery and also contributes to the development of anxiety-like and depression-like behaviors after stroke. Thus, PTP1B may represent a novel therapeutic target to improve stroke recovery. All procedures for animal use were approved by the Animal Care and Use Committee of the University of Ottawa Animal Care and Veterinary Service (protocol 1806) on July 27, 2018.Key Words: adhesive removal test, anxiety, depression, elevated plus maze, forced swimming test, Iba1, interleukin-1β, microglia, open field test, tail suspension test, tumor necrosis factor-α

Chinese Library Classification No. R453; R741; R364.5     

经输尿管导管逆行肾盂灌注凝血酶治疗大鼠肾穿刺后肾出血

建立肾穿刺术后持续性肉眼血尿的动物模型.经输尿管导管逆行肾盂灌注凝血酶,观察其止血效果,对肾功能及凝血功能的影响,并探讨最佳止血效果的凝血酶剂量.     

急性脑梗死血清C-反应蛋白的临床分析

目的观察急性脑梗死患者血清CRP在发病中的作用及临床意义。方法采用免疫比浊法对60例急性脑梗死患者的血清CRP水平进行动态观察（病程第1．7及14天），并与45例健康人进行比较。结果急性脑梗死患者血清CRP从病程第1天即升高（P〈0．01），至第7天达高峰，以后降低；重型患者明显高于轻、中型患者。结论血清CRP可能在急性脑梗死的发生、发展中起一定作用，并与病情严重程度呈正相关。     

全程分期式健康教育对Miles术后患者生活质量的影响

目的探讨全程分期式健康教育对Miles术患者生活质量的影响.方法将80例行Miles术的直肠癌患者随机分为观察组与对照组各40例.观察组采用全程分期式健康教育,对照组采用传统的手术前后宣教.两组均在出院前,出院后1、3、6个月发放Miles术患者生活质量问卷,在出院前发放护理工作满意度调查表进行调查.结果观察组出院前自理能力、造口情况、心理状况及护理工作满意度显著优于对照组(P＜0.05,P＜0.01),出院时间显著缩短(P＜0.05);出院后观察组自理能力、造口情况等及生活质量总分均显著优于对照组(P＜0.05,P＜0.01).结论全程分期式健康教育能有效提高Miles术患者的近期和远期生活质量.     

前置胎盘孕妇恐惧心理观察及护理

目的观察前置胎盘孕妇的恐惧心理反应，做好前置胎盘孕妇的心理护理。方法由孕妇自行填写CES-D和SA2量表，进行统计学分析。结果70．2％的前置胎盘孕妇具有恐惧心理。结论在妊娠过程应提高孕妇认知水平，加强心理护理，有助于她们顺利渡过妊娠期。     

后牙两段式可摘局部义齿的设计与制作

目的:改进常规可摘局部义齿设计的不足,增进固位、稳定。方法:采用两段式义齿结构、两个就位方向和插销锁连接固定。结果:义齿的固位、稳定效果明显提高。结论:插销式分段义齿是对常规可摘局部义齿的一种补充,对主基牙过度倾斜、固位要求高的患者,能够明显改善修复效果。     

Measurement of alveolar derecruitment in patients with acute lung injury: computerized tomography versus pressure–volume curve

Introduction  

Positive end-expiratory pressure (PEEP)-induced lung derecruitment can be assessed by a pressure–volume (P–V) curve method or by lung computed tomography (CT). However, only the first method can be used at the bedside. The aim of the study was to compare both methods for assessing alveolar derecruitment after the removal of PEEP in patients with acute lung injury or acute respiratory distress syndrome.     

β-胡萝卜素立体异构体对环磷酰胺处理小鼠免疫功能的比较研究

就β-胡萝卜素立体异构体对环磷酰胺处理小鼠的免疫功能影响进行了比较研究。结果显示β-胡萝卜素立体异构体对外磷酰胺造成的免疫功能低下具有不同程度的改善作用，提高胸腺和脾脏指数，增强脾脏细胞对刀豆素A（ConA）的反应性和NK活性，血清溶菌酶含量也有所增加。综合各项指标，9-顺式和全反式混合物的作用最明显，提示一定浓度的9-顺式对于提高β-胡萝卜素对机体的总体作用是有一定意义的。     

L-丙酰肉碱对再灌注心肌损伤的保护及体外抗自由基作用

目的:观察L－丙酰肉碱对缺血再灌注心肌的保护作用，并探讨其机理。方法：采用大鼠在体心脏冠状动脉前降支阻断5min造成缺血再灌注模型，持续心电监护，观察心律失常与心功能指标；应用电子顺磁共振观察L－丙酰肉碱对Fenton体系及二甲基亚砜（DMSO）碱性有氧体系产生自由基的作用。结果：L－丙酰肉碱静脉给药明显减少再灌注时室性心动过速、室性纤维颤动的发生（P＜0．05），促进再灌注后左室收缩压、左室压最大上升速率、左室压最大下降速率、心力环面积的恢复，与对照组相比，各参数均明显增高（P＜0．05）；静脉注射L－丙酰肉碱100mmol／L时促进Fenton体系OH的产生，而500mmol／L时产生明显抑制作用，L－丙酰肉碱明显抑制DMSO碱性有氧体系OS的产生。结论：L－丙酰肉碱明显减少再灌注心律失常的发生，促进再灌注后心功能的恢复。推测它对自由基的作用可能是再灌注损伤保护机理之一。     

发育期大鼠高热惊厥前后海马γ-氨基丁酸B受体亚基表达的变化

目的：研究高热惊厥(febrile seizures，FS)对发育期大鼠脑内γ-氨基丁酸(γ-aminobutyric acid，GABA)B受体亚基GABABR1与GABARR2蛋白表达的影响。方法：采用热水浴诱导大鼠高热惊厥模型。隔日诱导惊厥1次，共诱导10次，末次惊厥后24h处死大鼠。发育期大鼠随机分为3组：对照组(n＝24)，1次高热处理组(n＝28)，10次高热处理组(n＝40)。高热处理组根据是否出现惊厥再分为1次高热惊厥组(FS1，n＝16)与1次高热未惊厥组(F1，n＝12)，10次高热惊厥组(FS10，n＝15)与10次高热未惊厥组(F10，n＝13)。采用免疫组化方法观察不同次数高热惊厥大鼠脑内GABABR1与GABABR2蛋白表达的变化。结果：FS10大鼠海马齿状回、CAl-CA3区GABABRl和GABABR2蛋白表达明显低于F10、F1、FSl和对照组；F10大鼠上述脑区GABABRl和GABABR2蛋白表达低于F1、FS1和对照组；F1及FS1大鼠与对照组相比差异无显著性；海马各区GABABR1与GABABR2表达的改变大部分平行，但10次高热惊厥后GABABR2在CA1—CA3区下降更明显，而GABABR1在齿状回下降更明显。结论：反复高热惊厥及反复高热均可使发育期大鼠脑内GABABR亚基蛋白表达降低，高热惊厥的影响较单纯高热更为明显，提示GABABR亚单位与发育期大鼠高热惊厥及其脑损伤密切相关。GABABR1与GABABR2改变的不平行可能与受体亚单位组合的可塑性改变有关，这种改变可能导致抑制功能的改变。