阿尼西坦对血管性痴呆大鼠的治疗作用

目的: 探讨阿尼西坦(Ani)对血管性痴呆(VD)大鼠的治疗作用。方法: 实验将45只大鼠随机分为对照组、模型组和Ani治疗组。采用改良四血管阻断法(永久灼闭椎动脉、可逆夹闭颈总动脉)建立VD大鼠模型,用Ani(300 mg/kg)灌胃治疗4周;对照组大鼠手术同上,但不阻断血供,生理盐水2 ml灌胃4周。4周后行Morris水迷宫实验,测试各组大鼠空间学习记忆能力;采用免疫组化法检测半胱氨酸天门冬氨酸蛋白酶-3(caspase-3)在海马齿状回的表达。结果: Ani组大鼠学习记忆能力较模型组明显提高(P＜0.05),caspase-3在海马齿状回的表达水平比模型组明显降低(P＜0.05)。结论: Ani能增强VD大鼠的空间认知能力,机制可能与其下调caspase-3表达而保护海马细胞免受凋亡损伤有关。     

电针降低氯胺酮大鼠岛叶皮质和尾壳核c-Fos水平

目的为了证明电针是否对氯胺酮滥用大鼠岛叶皮质(insular cortex,IC)和尾壳核(caudate putamen,CP)c-Fos表达产生影响。方法将32只清洁级SD大鼠采用随机数字表法,分为正常组、生理盐水组、模型组(氯胺酮腹腔注射)和电针组(氯胺酮+电针一侧"三阴交"和"足三里"穴)。采用免疫组织化学方法检测IC和CP内c-Fos表达。结果与正常组、生理盐水组相比,模型组大鼠出现鼠尾僵直上翘、扭体等兴奋症状;IC和CP内c-Fos阳性细胞数明显增多;与模型组相比,电针组大鼠兴奋症状明显减少;IC和CP内c-Fos阳性细胞数明显减少。结论电针对氯胺酮滥用所致的IC和CP内c-Fos表达增强具有下调作用。     

电针及天麻素降低脑缺血大鼠杏仁中央核Nago-A及其受体的免疫组织化学表达

目的观察电针及天麻素对脑缺血大鼠杏仁中央核(central nucleus of amygdale,CeA)神经轴突生长抑制因子A(neurite outgrowth inhibitor-A,Nogo-A)及其受体(Nogo-A receptor,NgR)水平的影响,了解Nago-A及其受体是否参与针药结合治疗脑缺血作用。方法将SD大鼠随机分为正常组、模型组、电针组、天麻素组和电针+天麻素组。除正常组,其余组采用线栓法复制局灶性脑缺血大鼠模型。待造模成功大鼠清醒后,模型组不予治疗,电针组电针(频率2Hz)刺激左侧"曲池""合谷"穴,天麻素组腹腔注射天麻素注射液,电针+天麻素组给予电针和天麻素联合治疗;均为每天1次,共治疗14d。采用免疫组织化学方法检测CeA内Nogo-A、NgR蛋白的水平。结果模型组Nogo-A、NgR免疫组织化学表达较正常组明显增强,电针组、天麻素组和电针+天麻素组Nogo-A和NgR表达性较模型组明显减弱,电针+天麻素组Nogo-A、NgR表达较电针组或天麻素组减弱。结论电针及天麻素均可抑制脑缺血后CeA内Nogo-A、NgR水平的升高,二者结合具有协同作用。     

大鼠脑出血后大脑凝血酶受体-1长时效动态表达变化

目的:探讨脑出血(ICH)后凝血酶受体的动态及长时效表达。方法:将36只大鼠随机分为6组(n=6):正常组,ICH模型6h、24h、3d、7d和14d组。Ⅶ-S型胶原酶诱导大鼠ICH模型。免疫组化方法测定不同时间点大鼠ICH后血肿周围水肿组织PAR-1蛋白的表达;RT-PCR方法检测蛋白酶激活的受体(PAR)-1mRNA的表达。结果:正常组大鼠大脑PAR-1蛋白和PAR-1mRNA表达轻度阳性,模型组6h时PAR-1表达强度开始增强,24hPAR-1表达进一步增强,于3d达到高峰,然后开始下降,7d时明显下降,14d进一步下降,但仍未至正常组水平。模型组各时间点PAR-1阳性细胞数、PAR-1mRNA吸光度比值升高与正常组比较均有显著性差异(P<0.05或P<0.01)。此外,PAR-1蛋白在脑微血管内皮细胞在体有明显的表达。结论:脑微血管内皮细胞存在PAR-1,ICH后凝血酶激活PAR-1不仅是ICH后脑水肿产生的始动因素,而且参与了脑水肿的发展过程。     

骨髓间充质干细胞对大鼠急性肾损伤的修复作用

目的:观察外源性骨髓间充质干细胞(Mesenchymal stem cells,MSCs)对庆大霉素(Gentamycin,GM)诱导的大鼠急性肾损伤是否具有治疗作用,并初探其机制。方法:建立腹腔注射庆大霉素致大鼠急性肾损伤模型实验分为正常对照组、模型组、MSCs治疗组(模型+MSCs)、生理盐水组(模型+生理盐水)。于不同处理后4d分别检测血尿素氮(BUN)和肌酐(Scr)水平,观察肾组织病理改变,免疫印迹及RT-PCR法检测肾组织肝细胞生长因子(Hepatocyte growth factor,HGF)水平。结果:模型组大鼠的BUN及Scr较正常对照组显著升高,且肾小管组织病理损伤严重;而MSCs治疗组大鼠的BUN及Scr水平较生理盐水组显著降低,肾小管组织病理损伤明显减轻。此外,促肾小管损伤修复的肝细胞生长因子(HGF)表达在MSCs治疗组显著高于生理盐水组。结论:MSCs输注可促进庆大霉素所致急性肾小管损伤的修复,改善肾功能,其作用机制可能是与上调肾组织中肝细胞细胞生长因子的表达有关。     

右心导管法测大鼠肺动脉压力的改良

目的:目前常用的测量大鼠肺动脉压力的右心导管法存在一定的缺陷,且很难得到典型的压力曲线图。本实验对大鼠经颈外静脉插管与测压的方法进行改良,同时与已有报道的实验结果进行比较,并提供正常SD大鼠右心房、右心室及肺动脉的压力参考值及典型的压力曲线图,以协助研究人员判断导管位置,及时调整导管的深度和方向,快速测出肺动脉压力。方法:雌雄不分的清洁级SD大鼠共30只,体重180~230 g,6~7周龄。应用自制的末端呈一弧形的PE-10管,采用改良后的右心导管法,经颈外静脉插入大鼠心腔及肺动脉,检测并计算大鼠右心房、右心室和肺动脉的收缩压、舒张压及肺动脉平均压。结果:右心房压力波动较平缓,呈小波浪形;右心室压力曲线波动大,骤升骤降;肺动脉压力曲线有重搏波。正常SD大鼠右心房舒张压为(2.03±2.56)mmHg,收缩压为(2.82±1.85)mmHg;右心室舒张压为(5.72±3.99)mmHg,收缩压为(18.73±4.80)mmHg;肺动脉舒张压为(15.27±2.64)mmHg,收缩压为(18.49±2.53)mmHg,肺动脉平均压为(16.34±2.32)mmHg。右心室收缩压与肺动脉收缩压无明显差异(P0.05)。结论:改良后的方法可准确到达大鼠肺动脉,提供的压力参考值及曲线图有助于研究人员顺利完成测压实验。     

杏仁核SIRT1对慢性束缚应激大鼠抑郁样行为的影响

目的:观察杏仁核沉默信息调节因子1(SIRT1)蛋白对慢性束缚应激(CRS)大鼠抑郁样行为的影响。方法:60只SD雄性大鼠随机分为6组(n=10):正常对照组(Control)、慢性束缚应激组(CRS)、CRS+氟西汀(FLU)组(CRS+FLU)、CRS+生理盐水组(CRS+NaCl)、CRS+SIRT1过表达组(CRS+AAV-SIRT1)和CRS+空载体组(CRS+AAV-EGFP)。除了正常对照组,其余各组均接受慢性束缚应激造模21 d。造模结束后,氟西汀组和生理盐水组大鼠每天分别灌胃给予氟西汀(10 mg/kg)或生理盐水(10 mg/kg),持续3周;SIRT1过表达组和空载体组大鼠分别脑立体定位,注射腺相关病毒AAV-SIRT1或AAV-EGFP于杏仁核,待病毒表达3周;正常组和抑郁症组大鼠则不给予任何药物。应用糖水偏好实验(SPT)、旷场实验(OFT)和强迫游泳实验(FST)检测各组大鼠的抑郁样行为学变化;蛋白免疫印迹实验检测大鼠杏仁核中SIRT1蛋白的表达;免疫荧光技术检测大鼠杏仁核中SIRT1阳性细胞数量。结果:与正常对照组相比,CRS抑郁大鼠杏仁核中SIRT1蛋白...     

布地奈德吸入对哮喘气道重塑大鼠气道平滑肌细胞MMP-9及TIMP-1表达的影响

目的探讨布地奈德气雾剂对哮喘气道重塑大鼠气道平滑肌细胞(airway smooth muscle cell,ASMC)中MMP-9(金属基质蛋白-9)及TIMP-1mRNA(组织抑制因子-1)表达的影响。方法将60只wistar大鼠按照随机分组原则分为正常组、模型组及治疗组。模型组采用Wistar大鼠哮喘模型制作方法制作哮喘气道重塑大鼠模型;HE染色图像分析测量各组大鼠肺组织中气道壁面积(Wat)及平滑肌层面积(Was),并用气道基膜周长(Pbm)进行标准化;原代培养各组大鼠ASMC;实时定量PCR检测比较各组大鼠ASMC中MMP-9及TIMP-1mRNA表达含量,用SPSS 17.0统计软件进行统计学分析,组间比较采用单因素方差分析,P<0.05为差异有统计学意义。结果模型组大鼠肺组织中Wat/Pbm及Was/Pbm明显较正常对照组增加,治疗组大鼠肺组织中Wat/Pbm及Was/Pbm较正常对照组增加,但较模型组明显降低,差异均有统计学意义(P<0.05)。模型组大鼠ASMC中MMP-9mRNA表达较正常对照组增加,差异有统计学意义(P<0.05);但治疗组大鼠ASMC中MMP-9mRNA表达较模型组减少,差异有统计学意义(P<0.05);但较正常对照组大鼠ASMC中含量增加(P<0.05)。模型组大鼠ASMC中TIMP-1mRNA表达较正常对照组降低;但治疗组大鼠ASMC中TIMP-1mRNA表达较哮喘组增加,但较正常对照组降低(P<0.05)。结论布地奈德通过降低哮喘大鼠ASMC中MMP-9mRNA,增加TIMP-1mRNA表达,从而减轻哮喘大鼠ASMC细胞间质增厚。     

多烯磷脂酰胆碱对β- 淀粉样蛋白（Aβ1-40）致阿尔茨海默病 模型大鼠的治疗作用

目的:研究多烯磷脂酰胆碱(Polyene Phosphatidyl choline,PPC)对β-淀粉样蛋白(Aβ1-40)致阿尔茨海默病(Alzheimer’s Dis-ease,AD)模型大鼠的治疗作用。方法:32只SD大鼠随机分为正常组、假手术组、模型组和处理组,海马内注射淀粉样蛋白(Aβ1-40),制作大鼠阿尔茨海默病模型,处理组给予多烯磷脂酰胆碱。通过Morris水迷宫实验验检测各组大鼠认知行为学改变,海马组织学及免疫组化染色,观察多烯磷脂酰胆碱对阿尔茨海默病模型大鼠的影响,并进行统计学分析。结果:①Morris水迷宫实验,模型组与正常组、假手术组比较,学习和记忆潜伏期显著增加;处理组与模型组比较,学习和记忆潜伏期显著减少;组间比较差异有统计学意义(P<0.05),提示多烯磷脂酰胆碱使AD模型大鼠的认知行为学功能改善。②Nissl染色,模型组与正常对照组、假手术组组织学染色结果有显著性差异(P<0.05),PPC处理组与模型组比较有显著性差异(P<0.05),PPC处理组与正常组及假手术组比较也呈现出显著性差异(P<0.05);提示多烯磷脂酰胆碱可以减少神经元的凋亡。③β-淀粉样蛋白免疫组化染色,模型组与正常对照组、假手术组比较,Aβ沉积明显增加;PPC处理组与模型组比较,Aβ沉积范围明显缩小,PPC处理组与正常对照组、假手术组也呈现出显著性差。结论:多烯磷脂酰胆碱对淀粉样蛋白(Aβ1-40)致阿尔茨海默病模型大鼠有治疗作用。     

TAA 致慢性肝病内毒素血症大鼠清道夫受体、CD14 表达变化*

目的:观察清道夫受体(SR)和脂多糖受体CD14在TAA介导的慢性肝病内毒素血症大鼠肝组织中的表达。方法:通过大鼠持续灌胃给小剂量(12mg/kg.d)TAA建立大鼠肝损伤内毒素血症模型,HE染色光镜观察肝脏病理变化;改良赖氏法检测大鼠血清ALT、AST;改良过氯酸法测定血清内毒素含量;酶联免疫法检测大鼠血清CD4+和CD8+;免疫组化染色方法观察大鼠肝组织清道夫受体和CD14的表达。结果:TAA诱导后,大鼠肝脏出现片状坏死并可见灶性炎症;血浆ALT、AST及内毒素水平显著升高(P<0.05或P<0.01);血清CD4+、CD8+T细胞明显降低(P<0.01);肝组织CD14表达上调,清道夫受体表达下调,和正常大鼠相比,差异显著(P<0.05)。结论:肝组织SR表达下降和CD14表达增强可能是TAA介导慢性肝病内毒素血症的重要机制。     

Isolation versus grouped housing in rats: Differential effects of low doses of heroin in the place preference paradigm

Male Long Evans rats were reared from weaning (21–23 days) either in isolation or in groups of four for 40 days. Animals were then individually introduced to a testing apparatus consisting of two distinct chambers. A modified place preference paradigm was used consisting of 3 phases: (1) An habituation phase (4 days) during which rats were allowed free access to the entire test apparatus for 15 min. periods daily; (2) A conditioning phase (4 days) during which rats were confined to their non-preferred side for 15 minutes each day immediately following subcutaneous injection of 0, 20, 40 and 80 μg/kg of heroin HCl; (3) A test phase (1 day) during which rats were again allowed free access to the testing chamber following injection of vehicle. The difference in time spent on the conditioned side during habituation and test periods was determined. The group-reared rats showed similar effects for all doses of heroin whereas the same magnitude of drug effect was attained only at the highest dose used in the isolated rats. This differential sensitivity to heroin in the place preference paradigm is discussed in terms of the modification of behavioral effects of opiates by environmental influences.     

MCC950对脑出血大鼠神经损伤的作用*

目的: 研究NLRP3炎性小体抑制剂MCC950对脑出血(ICH)大鼠神经损伤的作用。方法: 72只SD大鼠随机分为3组(n=24):sham组、ICH组和MCC950组。ICH组和MCC950组采用自体非抗凝血注射方法建立大鼠脑出血模型后,给予MCC950组大鼠腹腔注射MCC950 10 mg/kg(2 mg/ml),连续给药3 d。模型建立72 h后,进行前肢放置实验、转角实验和mNSS评分,观察ICH大鼠神经功能情况;新鲜脑组织切片,观察血肿体积变化情况;HE染色,观察脑组织病理学改变情况;干湿比重法,观察脑组织水肿变化情况;FJC染色,观察神经元退化的情况;TUNEL染色,观察神经元凋亡情况;Western blot,观察NLRP3、ASC、caspase-1、IL-1β、IL-18、GSDMD蛋白表达及激活水平的情况。结果: 与sham组比较,ICH组大鼠左前肢放置成功百分比和左侧转身百分比显著下降(P＜0.01,P＜0.05),mNSS评分显著升高(P＜0.01),右侧脑内血肿体积显著增大,血肿周围脑组织中小胶质细胞数量增加,神经元数量减少,神经细胞肿胀,排布不均,部分细胞固缩性坏死,染色加深,右侧基底部含水量显著增多(P＜0.05),血肿周围脑组织中FJC阳性和TUNEL阳性细胞数量显著增加(P＜0.05),NLRP3、ASC、caspase-1、pro-caspase-1、caspase-1/pro-caspase-1比值、GSDMD-N、GSDMD、GSDMD-N/GSDMD比值、IL-1β和IL-18水平显著升高(P＜0.01,P＜0.05)。与ICH组比较,MCC950组大鼠左前肢放置成功百分比和左侧转身百分比显著升高(P＜0.05),mNSS评分显著降低(P＜0.01),右侧脑内血肿体积显著减小,血肿周围脑组织中神经细胞肿胀显著减轻,固缩坏死细胞数量减少,右侧基底含水量显著减少(P＜0.05),血肿周围脑组织中FJC阳性和TUNEL阳性细胞数量显著减少(P＜ 0.05),NLRP3、ASC、caspase-1、pro-caspase-1、caspase-1/pro-caspase-1比值、GSDMD-N、GSDMD、GSDMD-N/GSDMD比值、IL-1β和IL-18水平显著降低(P＜0.05)。结论: MCC950可以通过抑制NLRP3炎性小体介导的炎症反应和细胞焦亡改善ICH后的神经损伤。     

Treatment of intracerebral haemorrhage in rats with intraventricular transplantation of human amniotic epithelial cells

We explored the effects on brain oedema and neurological functional recovery after transplantation of hAECs (human amniotic epithelial cells) into the lateral ventricle of rats with ICH (intracerebral haemorrhage). hAECs were isolated from human term placenta and seeded for primary culture. We delivered hAECs labelled with Hoechst33258 and transfected with EGFP (enhanced green fluorescent protein) gene using lentiviral vectors into ICH rat models. The behaviour of the animals and brain oedema were evaluated after 28 days, and brain sections were made for morphological and immunohistochemical analyses with fluorescence microscopy. Our results were as follows. Transplanted hAECs were observed along the lateral wall and survived for at least 4 weeks. Some of the cells were stained with human specific antibody to vimentin and nestin. Around the injury site, activated microglia stained with OX42 were reduced. The water content of ICH rats decreased in the treatment group. The behaviour test scores were improved in the treatment group compared with those in the control groups. In conclusion, hAECs cannot only survive in the lateral ventricle of ICH rats after transplantation, but also express vimentin and nestin. hAEC transplantation reduced brain oedema and improved the motor deficits of ICH rats.     

反复电刺激大鼠上矢状窦后的抑郁行为学表现

目的 观察反复电刺激清醒状态下大鼠上矢状窦后的行为学表现.方法 24只雄性SD大鼠随机分为对照组和实验组,实验组连续给予21d电刺激(电流1～2 mA、频率20 Hz、正弦波,脉冲宽度250 μs,持续15分钟/次,1次/天),通过观察大鼠体重变化、液体消耗实验及旷场实验来评价大鼠是否抑郁.结果 电刺激21d后,实验组较对照组大鼠体重增长减慢(P＜0.05),其差别有统计学意义;实验组旷场实验得分、液体消耗实验中糖水消耗量和蔗糖偏嗜度均明显下降,与对照组相比有统计学差异(P＜0.05);而纯水消耗量显著升高(P＜0.05).结论 21d反复电刺激清醒状态下大鼠上矢状窦,大鼠有抑郁的行为学表现.     

ICH-harmonised guidances on genotoxicity testing of pharmaceuticals: evolution, reasoning and impact.

The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has convened an expert working group which consisted of the authors of this paper and their respective committees, consulting groups and task forces. Two ICH guidances regarding genotoxicity testing have been issued: S2A, 'Guidance on Specific Aspects of Regulatory Genotoxicity Tests' and S2B, 'Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals.' Together, these guidance documents now form the regulatory backbone for genotoxicity testing and assessment of pharmaceuticals in the European Union, Japan, and the USA. These guidances do not constitute a revolutionary new approach to genotoxicity testing and assessment, instead they are an evolution from preexisting regional guidelines, guidances and technical approaches. Both guidances describe a number of specific criteria as well as a general test philosophy in genotoxicity testing. Although these guidances were previously released within the participating regions in their respective regulatory communiqués, to ensure their wider distribution and better understanding, the texts of the guidances are reproduced here in their entirety (see Appendix A) and the background for the recommendations are described. The establishment of a standard battery for genotoxicity testing of pharmaceuticals was one of the most important issues of the harmonisation effort. This battery currently consists of: (i) a test for gene mutation in bacteria, (ii) an in vitro test with cytogenetic evaluation of chromosomal damage with mammalian cells or an in vitro mouse lymphoma tk assay, (iii) an in vivo test for chromosomal damage using rodent hematopoietic cells. A major change in testing philosophy is the acceptance of the interchangeability of testing for chromosomal aberrations in mammalian cells and the mouse lymphoma tk assay. This agreement was reached on the basis of the extensive review of databases and newly generated experimental data which are in part described in this publication. The authors are fully aware of the fact that some of the recommendations given in these ICH guidances are transient in nature and that the dynamic qualities and ongoing evolution of genetic toxicology makes necessary a continuous maintenance process that would serve to update the guidance as necessary.     

脑出血大鼠血肿周围脑组织含水量与MMP-9、IL-6及TIMP-1表达水平的相关性研究

目的:研究脑出血(ICH)大鼠血肿周围脑组织含水量与基质金属蛋白酶-9(MMP-9)、白细胞介素-6(IL-6)及组织基质金属蛋白酶抑制剂-1(TIMP-1)表达水平的相关性。方法:84只健康成年雄性Wistar大鼠按随机数字表法分成观察组、假手术组以及对照组,每组28只。另将观察组分成ICH后1d亚组9只,3d亚组9只,7d亚组10只。观察组大鼠实施ICH模型的制备,假手术组的大鼠仅给予空针穿刺,对照组不进行模型制备。检测并对比各组血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1水平,对比观察组内不同亚组(ICH后1d、3d、7d)血肿周围的脑组织含水量、MMP-9、IL-6和TIMP-1水平,并分析ICH大鼠血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1表达水平的相关性。结果:观察组血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1水平均分别高于假手术组及对照组,差异均有统计学意义(P0.05)。观察组内3d和7d亚组血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1水平均分别高于1d亚组,但7d亚组低于3d亚组,差异均有统计学意义(P0.05)。根据Spearman相关性分析结果显示,ICH大鼠血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1表达水平均呈正相关(P0.05)。结论:ICH大鼠的血肿周围脑组织含水量与MMP-9、IL-6及TIMP-1表达水平均呈正相关,MMP-9、IL-6、TIMP-1在ICH后周围组织水肿的发生、发展中具有重要作用。     

ICH-Harmonised guidances on genotoxicity testing of pharmaceuticals: evolution,reasoning and impact

The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has convened an expert working group which consisted of the authors of this paper and their respective committees, consulting groups and task forces. Two ICH guidances regarding genotoxicity testing have been issued: S2A, `Guidance on Specific Aspects of Regulatory Genotoxicity Tests' and S2B, `Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals.' Together, these guidance documents now form the regulatory backbone for genotoxicity testing and assessment of pharmaceuticals in the European Union, Japan, and the USA. These guidances do not constitute a revolutionary new approach to genotoxicity testing and assessment, instead they are an evolution from preexisting regional guidelines, guidances and technical approaches. Both guidances describe a number of specific criteria as well as a general test philosophy in genotoxicity testing. Although these guidances were previously released within the participating regions in their respective regulatory communiqués, to ensure their wider distribution and better understanding, the texts of the guidances are reproduced here in their entirety (see Appendix A) and the background for the recommendations are described. The establishment of a standard battery for genotoxicity testing of pharmaceuticals was one of the most important issues of the harmonisation effort. This battery currently consists of: (i) a test for gene mutation in bacteria, (ii) an in vitro test with cytogenetic evaluation of chromosomal damage with mammalian cells or an in vitro mouse lymphoma tk assay, (iii) an in vivo test for chromosomal damage using rodent hematopoietic cells. A major change in testing philosophy is the acceptance of the interchangeability of testing for chromosomal aberrations in mammalian cells and the mouse lymphoma tk assay. This agreement was reached on the basis of the extensive review of databases and newly generated experimental data which are in part described in this publication. The authors are fully aware of the fact that some of the recommendations given in these ICH guidances are transient in nature and that the dynamic qualities and ongoing evolution of genetic toxicology makes necessary a continuous maintenance process that would serve to update the guidance as necessary.     

Hormonal regulation of maternal behavior in rats: stimulation following treatment with ectopic pituitary grafts plus progesterone

Changes in hormone secretions during pregnancy help to stimulate the onset of maternal behavior at parturition. To date, studies have demonstrated that estradiol (E2) appears to be a necessary component in the hormonal induction of maternal behavior in rats and other mammals. In the present study, we have reevaluated the contribution of E2, progesterone (P), and hormone-secreting pituitary grafts in the rapid induction of maternal behavior by measuring the behavioral effects of exposure to various combinations of P and prolactin-secreting ectopic pituitary grafts in the absence of estrogen. Adult hypophysectomized and nonhypophysectomized nulliparous rats were ovariectomized 2-3 days (Treatment Day 1) after their arrival in our laboratory. In Experiment #1, experimental, hypophysectomized rats were implanted s.c. with 6 P-filled Silastic capsules and given 2 anterior pituitary (AP) glands that were grafted beneath the kidney capsule on Treatment Day 1. Controls were given blank implants and were sham-grafted. P-filled and blank Silastic capsules were removed on Day 11, and behavioral testing was conducted once-a-day beginning on Day 12 for eleven days. Animals treated with P-plus-pituitary grafts displayed full maternal behavior significantly faster than did controls (median latencies of 3.0 and 7.5 days, respectively). In Experiment #2, nonhypophysectomized rats were assigned to one of three treatments. On Treatment Day 1, one group of rats received 6 P-filled Silastic implants and had 2 AP glands grafted under their renal capsules. A second group of animals received 6 P capsules and was sham-grafted, while controls were given blank implants and were sham-grafted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Possibilities and Prospects of the Behavioral Test “Morris Water Maze”

Journal of Evolutionary Biochemistry and Physiology - The Morris Water Maze (MWM) behavioral test is a universal method for testing cognitive functions in experimental rodents, and it is especially...     

SRC-3 Deficiency Exacerbates Neurological Deficits in a Mouse Model of Intracerebral Hemorrhage: Role of Oxidative Stress

Intracerebral hemorrhage (ICH) causes long term neurological abnormality or death. Oxidative stress is closely involved in ICH mediated brain damage. Steroid receptor cofactor 3 (SRC-3), a p160 family member, is widely expressed in the brain and regulates transactivation of Nrf2, a key component of antioxidant response. Our study aims to test if SRC-3 is implicated in ICH mediated brain injury. We first examined levels of SRC-3 and oxidative stress in the brain of mice following ICH and analyzed their correlation. Then ICH was induced in wild type (WT) and SRC-3 knock out mice and how SRC-3 deletion affected ICH induced brain damage, oxidative stress and behavioral outcome was assessed. We found that SRC-3 mRNA and protein expression levels were reduced gradually after ICH induction in WT mice along with an increase in oxidative stress levels. Correlation analysis revealed that SRC-3 mRNA levels negatively correlated with oxidative stress. Deletion of SRC-3 further increased ICH induced brain edema, neurological deficit score and oxidative stress and exacerbated ICH induced behavioral abnormality including motor dysfunction and cognitive impairment. Our findings suggest that SRC-3 is involved in ICH induced brain injury, probably through modulation of oxidative stress.