不同剂量骨疏灵和不同强度运动联合应用对去势大鼠骨生物力学的影响*★

目的：观察不同剂量中药骨疏灵和不同强度运动联合应用对去卵巢大鼠骨生物力学的影响，确定适合的运动强度和中药剂量。 方法：实验于2006-01在四川大学高分子实验室完成。3个月龄健康雌性SD大鼠70只，体质量（250±20）g。驯化喂养15 d后分别称体质量，随机设计法将大鼠分为假手术组、模型对照组、己烯雌酚阳性对照组、低强度运动加中剂量中药组、低强度运动加高剂量中药组、中强度运动加中剂量中药组和中强度运动加高剂量中药组，每组10只。手术切除各实验组大鼠双侧卵巢。术后1周，各组大鼠无异常，实验参照Bedford的动物负荷标准，中药和运动方案各组大鼠术后第7天起在小动物跑台上开始训练。按不同要求进行实验，12周后麻醉并处死大鼠，取第3腰椎进行生物力学指标检测。组间比较采用单因素方差分析，组间差异采用LCD检验，采用2×2析因实验分析，确定有无交互作用，以及交互作用的显著性水平，分析指标为骨生物力学敏感指标，确定中药和运动组合优选方案。 结果：纳入SD大鼠70只，进入结果分析67只，其中模型对照组死亡2只，中强度运动加高剂量中药组死亡1只。①析因分析：生物力学各指标的变化基本呈一致性趋势。能量吸收、弹性模量、最大应变、结构刚度4个指标析因分析显示，单纯运动和单纯中药作用明显（P < 0.05）；中药和运动的交互作用不明显（P > 0.05），表现为相加效应。②组间比较：中强度运动加高剂量中药组生物力学各指标相对于其他联合组更接近于己烯雌酚阳性对照组和假手术对照组（P < 0.05）。其中弹性模量高于假手术对照组，能量吸收和最大载荷2个指标高于已烯雌酚阳性对照组，但差异均无显著性(P > 0.05)。 结论：中药骨疏灵和运动联合方案可延缓去势大鼠骨量的丢失，两者联合应用有累加效应。中强度运动加高剂量中药组在联合方案中显示出最佳效果。     

捆绑带束缚压力对骨折模型动物骨痂形成及愈合的影响

背景：有些观点认为捆绑带的使用会影响骨折部位的血运甚至造成骨折延迟愈合与骨折不愈合。目的：观察3种不同束缚压力捆绑带对骨折动物模型骨痂形成及愈合的影响。方法：建立新西兰大白兔股骨干非负重骨折动物模型,髓内固定后随机分为3组,分别在骨折部位加用200,150,100 N束缚压力的捆绑带固定,术后2,4,6周观察骨痂形成及愈合。结果与结论：200 N压力组骨折固定牢固,但骨折断端外骨痂形成受限,无骨愈合,影响断端远期稳定性。100 N压力组早期骨折断端不稳定,虽不影响骨折愈合,但容易出现畸形愈合。150 N压力组压力适中,骨折固定与愈合均良好。提示在保持适当束缚压力的情况下,捆绑带可以有效维持骨折部位稳定,避免骨折移位或畸形愈合,保障骨折正常愈合,对骨折部位骨膜血运无异常影响,有助于促进骨折早期愈合。     

Ludloff截骨治疗拇外翻对前足底压力的影响

背景：目前Ludloff截骨术虽在国内外应用广泛,但对其造成具体的前足底生物力学改变研究较少。 目的：了解Ludloff截骨造成足底压力分布的改变,并进一步推测其特点及适应证。 方法：实验组选取拇外翻患者11例15足,行第1跖骨远端软组织松解、近端改良 Ludloff截骨术。对照组选取健康成人11名16足。对照组、实验组术前及术后6个月均采用Tekscan 足底压力测试系统进行动态测试,将前足底依5个跖骨头位置划分为5个研究区域,分别用Mn(1,2,3,4,5)表示。通过比较术前术后及对照组之间的区域压力峰值(PF)和区域压力总合(F)来评估足底压力变化。 结果与结论：F值：患者术前步态周期中,当第1跖骨头负荷达峰值时,通过第2跖骨的负荷最大,第1跖骨次之;而术后则为通过第1跖骨的负荷最大,第2跖骨次之;对照组则为通过第1,2跖骨的负荷最大,两者之间差异无显著性意义。各组中第3,4,5跖骨负荷均是由内向外依次递减。PF值：术前与对照组均表现为M2、 M1(M3)、M4、M5 依次递减;术后为M1(M2、M3)、M4、M5依次递减。M1/M2、M2/M3仅在术前与术后有明显差异。结果提示：①拇外翻患者足底压力的确存在外移,但主要是由第1跖骨移向第4、5跖骨。②Ludloff截骨术主要影响第1,2跖骨负荷,而对3,4,5跖骨影响较小。     

构建兔菜花耳模型和曲安奈德对耳郭的影响

背景：菜花耳主要是皮下的纤维组织增生，目前还没有找到一种令人满意的动物模型，曲安奈德常用于治疗增生性瘢痕和咬肌肥大，其是否也可以诱导其增生的组织萎缩呢？ 目的：构建菜花耳兔模型并观察注射曲安奈德对其增生性瘢痕的修复和治疗作用。 设计、时间及地点：随机对照动物实验；组织学观察，于2008-08/2009-02在广西中医学院动物实验中心进行。 材料：健康新西兰兔10只，耳郭没有异常，雌雄不限；曲安奈德注射液为昆明积大制药有限公司产品(国药准字53021604)。 方法：10只健康、耳郭正常的新西兰兔通过反复重物撞击耳郭造模，6轮实验后成功构建菜花耳模型，随机分为对照组和实验组，每组5只兔子(10只耳郭)。对照组在增厚的耳郭内注射利多卡因0.3 mL，实验组注射曲安奈德40 mg (1 mL)和利多卡因1 mL混合液0.3 mL，每3周1次，共3次，游标卡尺测量耳郭的厚度，实验结束进行组织病理检查。 主要观察指标：①两组兔大体观察。②耳郭厚度。③耳郭组织病理学观察。 结果：6轮实验后，全部的耳郭显著增厚变硬，造模成功，两组耳郭厚度差异无显著性意义，注射后实验组显著比对照组变薄变软。实验结束的组织病理检查，对照组的组织特点同菜花耳，皮下大量的纤维组织增生，组织致密；实验组可见药物残留，其周围的纤维组织变得疏松，有的出现变性、玻璃样变、胶原断裂和钙盐沉积；而离药物较远的位置纤维组织增生、更致密，同菜花耳治疗前。 结论：通过反复重物坠落撞击兔耳可构建菜花耳模型，局部注射曲安奈德可修复模型耳郭变薄变软。     

失用性骨质疏松动物承重骨的骨改建活动及其力学性能

背景：失用性骨质疏松由于肌肉不活动和负重减少引起骨量丢失。 目的：观察失用性骨质疏松发展过程中不同时间内骨的结构、矿物质含量以及受其影响骨生物力学性能的变化。 设计、时间及地点：对照观察动物实验于2003-09/11在天津医科大学总医院完成。 材料：雄性8月龄日本大耳白兔55只。 方法：选用雄性日本大耳白兔55只。随机取50只兔，石膏管型固定右后肢作为实验侧，左侧后肢不固定作为对照侧，另5只双侧后肢作为空白对照组饲养3个月。 主要观察指标：取双侧胫腓骨行力学试验,测定钙元素的含量。取双侧跖骨头以苏木精-伊红染色和Masson染色进行组织学观察。 结果：对于最大负荷、弹性模量和骨钙含量等指标，实验侧胫腓骨在不同固定时间的差别显著，实验侧和空白对照组间均有差别(P < 0.05);对照侧和空白对照组间的差别不显著(P > 0.05)。实验侧骨皮质变薄，孔隙增多，骨小梁稀疏、纤细并有多处断裂，髓腔扩大，破骨细胞数增多。Masson染色见随着失用时间延长，新生胶原量也在减少。对照侧和空白对照组跖骨头骨皮质较厚，孔隙较少，骨小梁排列紧密，结构正常。 结论：在失用性骨质疏松形成过程中，骨钙含量、骨整体生物力学性能持续下降，但速度趋缓，以适应所处应力环境和功能状态。     

糖尿病性骨质疏松患者血清自由基代谢与糖骨康的影响*

目的：糖尿病患者常伴有体内过氧化脂质水平的明显升高,而自由基增多可加重糖尿病并发症的发生和发展。糖骨康为治疗糖尿病骨质疏松症的临床验方，观察糖骨康对糖尿病骨质疏松患者骨密度、空腹血糖、糖化血红蛋白和血清超氧化物歧化酶、丙二醛含量的影响。 方法：①对象及分组：选择2003-03/2006-03在邯郸市第一医院老年病科和涉县中医院骨科收治的糖尿病骨质疏松患者139例。随机分为治疗组74例（年龄60~82岁），对照组65例（年龄60~85岁）。另设健康体检人员为正常组40名。上述人员对所用的治疗及检测指标均知情同意。③用药：治疗组服用中药糖骨康汤剂（由熟地黄、山萸肉、山药、锁阳、龟板、丹参、川芎组成，采用自动煎药机水煎包装）；对照组服用盖天力片(江苏启东盖天力制药厂生产)，两组同时口服西药常规降糖药，30 d为1疗程。④评估：治疗前后检测两组患者空腹血糖、糖化血红蛋白变化；比较正常组与两组患者治疗前骨密度、超氧化物歧化酶活性、丙二醛含量的差异。 结果：①两组患者空腹血糖以及糖化血红蛋白的比较：与治疗前比较，两组治疗后空腹血糖以及糖化血红蛋白均明显下降（P < 0.05或P < 0.01），但两组治疗后比较差异无统计学意义（P > 0.05）。②两组患者骨密度的比较：与治疗前比较，两组治疗后骨密度均明显上升（P < 0.05或P < 0.01），治疗组在升高骨密度方面优于对照组（P < 0.05）。③两组患者超氧化物歧化酶活性、丙二醛含量的比较：治疗后两组血清超氧化物歧化酶活性显著上升（P < 0.05或P < 0.01），丙二醛含量显著下降（P < 0.05或P < 0.01），治疗组在升高超氧化物歧化酶活性和降低丙二醛含量方面优于对照组（P < 0.05）。④正常组与治疗组、对照组患者骨密度、超氧化物歧化酶活性、丙二醛含量的比较：与正常组比较，治疗组、对照组患者骨密度和血清超氧化物歧化酶活性显著降低，丙二醛含量显著升高（P < 0.01）。 结论：糖骨康具有调节糖尿病骨质疏松患者自由基代谢，降低血糖，抑制骨质疏松的作用。     

兔胫骨骨延长模型在低强度脉冲超声刺激条件下的骨再生与成熟

背景：实验证实,低强度脉冲超声有促进骨折愈合的作用。但低强度脉冲超声对骨折愈合早期骨质再生成熟的影响及其相关的作用机制仍不十分清楚。 目的：创新性提出低强度脉冲超声能够在兔胫骨骨延长动物模型牵拉成骨早期骨再生成熟中发挥正效效应的理论假设,并期望以超声干预与不干预进行对照比较予以验证。 方法：36只成年健康新西兰兔随机数字表法分为超声治疗组和对照组,每组18只。所有动物均行胫骨中段截骨,以Orthofix M103型迷你外固定架延长器固定,术后7 d以0.5 mm/12 h延长10 d,总延长长度为10 mm,超声治疗组在延长完成后以低强度脉冲超声骨折治疗仪治疗,20 min/d,1次/d,对照组不给予低强度脉冲超声治疗。治疗4,8,12周后,X射线评定胫骨骨折断端愈合程度,采用Image J图像分析软件分析计算骨痂生成率;延长区新骨作苏木精-伊红染色、Masson三色染色、VG染色后光镜下组织学分析,并在显微镜下测新骨占总骨痂的面积。 结果与结论：36只兔均进入结果分析。治疗4周后对照组仅见外骨痂连接形成骨桥,骨痂区密度低,还可见部分骨痂缺如;超声治疗组骨早期再生成熟优于对照组,表现在两断端骨痂影密度增高,数量增多,骨痂影由两端向中央生长,被密度高的骨痂取代,外骨痂已开始被吸收,骨痂充满延长区,密度增高增粗,骨折处皮质骨密度接近正常皮质骨,骨痂生成率明显提高(P < 0.05),与8,12周无差异。组织学分析显示,超声治疗组治疗4,8,12周时新骨形成早于对照组,治疗4周新骨占总骨痂面积的百分比大于对照组,治疗8,12周后两组新骨占总骨痂面积的百分比无差别。提示低强度脉冲超声可促进新骨形成,增加骨痂面积,在兔胫骨骨延长动物模型牵拉成骨后的骨再生成熟中有促进作用。     

构建自体骨碎末移植材料修复骨缺损的实验模型★

学术背景：自体骨移植取材常需要开辟第二术区或在种植体周围取骨，额外增加创伤和感染机会，所以对局部小范围的骨质欠缺，可以考虑回收和利用预备种植体切除的自体骨末。 目的：建立恢复种植体周围骨缺损的自体骨碎末骨移植材料的实验模型，观察材料与宿主的生物相容性反应。 设计：单一样本观察。 单位：大连医科大学口腔医学院。 材料：实验于2005-08/2006-04在大连医科大学动物实验基地完成。实验动物为5只健康杂交家犬；种植体钛钉和Bio-Oss骨移植材料均由西安中邦钛生物材料有限公司设计制造并提供。 方法：拔除家犬下颌第1，2，3前臼齿，3个月后行种植术。预备种植体窝，每只犬左右两侧各预备4个，共40个。在每个种植窝内，各植入种植体钛钉1枚，共40枚。用种植转孔时收集的自体骨碎末、Bio-Oss骨移植材料及两者1∶1混合骨碎末恢复种植体颊侧单壁人为骨缺损，以未植骨作空白对照。 主要观察指标：①种植术后第9周时观察各组骨量的恢复情况、X射线片观察牙槽骨高度、骨小梁致密度及骨整合情况。②应用亚甲基蓝- 碱性品红法观察组织学变化。 结果：5只家犬钛钉无脱落，均纳入结果分析。①一般情况及骨缺损量：种植术后9周，创口愈合均良好，钛钉稳定，总存留率为100%。植入自体骨碎末的骨缺损量小于空白对照组（P < 0.01）；植入混合骨碎末的平均骨缺损量最小，说明恢复最佳。②骨量的恢复情况：X射线片显示40颗钛钉外周均与骨组织紧密接触，愈合良好。③材料与宿主的组织相容性：低倍镜下见所有钛钉均被周围淡红色的致密骨组织紧密包绕，种植体与骨组织间无蓝色的软组织，产生了直接骨结合界面。 结论：家犬建立自体骨碎末移植材料恢复种植体周围骨缺损的实验模型效果理想，材料与宿主间生物相容性好。     

肝细胞生长因子对心肌梗死后左心室收缩同步性的影响*

目的: 实验证实肝细胞生长因子可以促进心肌梗死后侧支循环形成，减少梗死面积，改善心脏功能。拟验证肝细胞生长因子（Hepatocyte growth factor， HGF）对急性心肌梗死后左心室重塑的影响。 方法： 实验于2005-06/2006-03在解放军总医院心内科实验室完成。①实验材料：pc-DNA3-HGF基因由军事医学科学院王立山副教授馈赠；杂种犬13只，雌雄不限，体质量15~20 kg。②实验分组：结扎犬左冠状动脉前降支复制急性心肌梗死模型，将造模成功的12只犬随机分为治疗组和对照组，每组6只。③实验过程：治疗组于梗死心肌周围注射pc-DNA3-HGF 1 mL (约300 μg)，对照组给予等量的生理盐水。④实验评估：分别于术后1，4，8周进行超声心动图检查，检测心功能、左室重塑指标。术后8周麻醉后处死动物，取出心脏，测量心脏及左心室重量，取心肌组织行苏木精-伊红染色；天狼猩红染色，并用图像分析系统测定梗死区、非梗死区及右室Ⅰ，Ⅲ型胶原含量；血管内皮细胞特异性Ⅷ因子免疫组织化学染色分析梗死区、非梗死区以及梗死边缘区血管生成情况；原位末端标记法染色观察细胞凋亡情况。实验过程中对动物处置符合动物伦理学标准。 结果：①术后 4周时，肝细胞生长因子治疗组左心室射血分数明显高于对照组（P < 0.05）；8周时，左心室射血分数明显升高，左心室收缩末容积较对照组降低（P < 0.05）。②心肌梗死后8周时治疗组左房面积、二尖瓣返流面积以及二尖瓣返流面积与左房面积的比值均低于对照组，心脏及左室重量指数亦低于对照组，但无统计学意义（P > 0.05）。③苏木精-伊红染色可观察到治疗组梗死心肌周围毛细血管较对照组增多，而对照组瘢痕形成明显。④Ⅷ因子免疫组织化学染色显示治疗组梗死边缘区毛细血管明显多于对照组（P < 0.01）；非梗死区毛细血管密度高于对照组（P =0.05）。⑤原位末端标记法染色显示与对照组相比，治疗组梗死边缘区凋亡细胞减少（P > 0.05）。 结论：肝细胞生长因子可能通过抑制梗死后的胶原沉积，增加梗死心肌周围毛细血管数目，减少细胞凋亡，使心肌坏死及瘢痕形成减少，从而缓解急性心肌梗死心室重塑及心功能的恶化。     

动脉粥样硬化模型动物脑血管的拉伸力学特性

背景：脑动脉粥样硬化和脑出血的防治有必要了解正常和动脑粥样硬化模型大鼠大脑中动脉的力学特性,但以往的研究对象多为正常人尸体与正常动物脑动脉的力学特性。 目的：比较正常和动脉粥样硬化动物模型大脑中动脉的拉伸力学特性。 方法：SD大鼠随机分为正常对照组和模型组。模型组大鼠建立动脉粥样硬化模型。取2组大鼠的大脑中动脉以电子万能试验机对其进行5 mm/min拉伸载荷实验,观察2组大鼠脑动脉最大载荷、最大位移、最大应力以及最大应变差异及血管应力-应变关系。 结果与结论：动脉粥样硬化大鼠脑动脉血管拉伸最大载荷、最大应力、最大位移及最大应变均较正常大鼠明显降低(P < 0.05),大鼠脑动脉血管应力-应变曲线是以指数关系变化的。因此,说明动脉粥样硬化模型大鼠大脑中动脉和正常对照组大鼠大脑中动脉具有不同的拉伸力学特性,脑动脉粥样硬化大鼠动脉血管不能像正常大鼠脑血管一样再作较大的伸展。     

Transcranial magnetic stimulation in animal models of neurodegeneration

Brain stimulation techniques offer powerful means of modulating the physiology of specific neural structures. In recent years, non-invasive brain stimulation techniques, such as transcranial magnetic stimulation(TMS) and transcranial direct current stimulation, have emerged as therapeutic tools for neurology and neuroscience. However, the possible repercussions of these techniques remain unclear, and there are few reports on the incisive recovery mechanisms through brain stimulation. Although se...     

Effect of teriparatide use on bone mineral density and spinal fusion: a narrative review of animal models

Purpose of the study: Teriparatide (Human recombinant Parathyroid Hormone 1-34) is an anabolic agent that is frequently used in patients with osteoporosis and has been extensively investigated with animal model and clinical studies in current literature. The purpose of the study was to evaluate the impact of teriparatide on bone mineral density and fusion.

Materials and methods: The findings from preclinical studies that have investigated the role of teriparatide in animal models are summarized in presented review.

Results: Overall, the studies show an improvement in bone mineral density and increased fusion rates for osteoporotic animals undergoing spine fusion with teriparatide use.

Conclusion: Further studies should be conducted for unanswered questions, such as teriparatide use before surgery, the effect on cervical fusion and surgery related complications.     

Application of magnetic resonance imaging in animal models of perinatal hypoxic-ischemic cerebral injury

Brain injury occurring in the perinatal period is an important etiology of subsequent neurodevelopmental disabilities. Magnetic resonance imaging (MRI) is a tool that is used to evaluate the nature of brain injury in the human infant. MRI techniques have also been applied to various animal models of perinatal injury. The most commonly used model is the immature rat, but there have also been imaging studies in mice, rabbit kits and piglets. The studies have been carried out using MR systems of various magnetic field strengths, ranging from 1.5 to 11.7tesla (T), with applications for quantification of infarct volume, T1 measurements, T2 measurements, proton and phosphorus spectroscopy and diffusion imaging. The MR findings are then related to histopathology and, in a few cases, behavioral evaluations. There is also a growing number of studies utilizing MRI in evaluating the efficacy of neuroprotective treatments, such as hypothermia.     

Thoughts on limitations of animal models

Animal models are a fundamental tool in the life sciences. They have advantages and disadvantages compared with other approaches. In a few instances, they represent the only reasonable approach. However, increasingly modern methods allow the 3R principle of reducing, refining and replacing animal experiments to be put into practice, as required wherever possible by European legislation. This article summarizes limitations typical of animal models. However, this does not mean that each and every limitation holds true for all animal models and that its alternatives have fewer limitations. A serious assessment of the models used is necessary to draw conclusions and make decisions in an evidence-based manner. Only by assessing the performance characteristics of any tool used in research, the results can be interpreted and the method employed can be complemented properly.     

Present status of magnetic resonance imaging and spectroscopy in animal stroke models.

Magnetic resonance imaging (MRI) is based on a wide variety of physical parameters, which, in principle, can all influence the image contrast conditions. As these diverse variables are validated by independent physiological, metabolic, hemodynamic, and histological techniques, a physiological MRI evolves. This imaging modality has been successfully applied to experimental stroke studies, covering a broad range of raised questions. In the present review, we present an overview of possible physiological criteria to be studied by in vivo MRI and magnetic resonance spectroscopy, and critically analyze the present limits and future potential of the imaging technique for experimental stroke investigations. The documented applications cover the spectrum from morphological-structural details of the lesion to hemodynamic and metabolic alterations, inflammatory reaction, evaluation of thrombolytic treatment, studies on recovery of functional brain activation by functional MRI, and, finally, the most recent applications of exploring stem cells for regenerative therapy.     

Cytokine and growth factor immunohistochemical spinal profiles in two animal models of mononeuropathy

Nerve injury leads to central neuroimmunologic responses that may be integral to the development and maintenance of chronic neuropathic pain in humans. Recent data have demonstrated that cytokines and growth factors may be strongly implicated in the generation of pain states at both peripheral and central nervous system sites. We utilized immunohistochemical methods to investigate this phenomenon in rat models of neuropathic pain. Specifically, we employed well-characterized models of neuropathy that result in behaviors suggestive of neuropathic pain in humans; a freeze lesion of the sciatic nerve, termed sciatic cryoneurolysis, and a chronic constriction sciatic nerve injury. We used immunohistochemistry to examine spinal localization of the cytokines, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and the growth factors, basic fibroblast growth factor (bFGF), and transforming growth factor-β1 (TGF-β) at 3, 14, and 35 days following sciatic cryoneurolysis or 6 days following chronic constriction injury as compared with normal, unoperated rats. There was minimal, diffuse cytokine/growth factor staining in lumbar spinal tissue from the normal group. However, cell profile quantification demonstrated increases in lumbar spinal IL-1β-, TNF-α- and TGF-β-like immunoreactivity (LI) in both mononeuropathy models studied. At 3 days following sciatic cryoneurolysis, intense bFGF LI was present in the ipsilateral dorsal and ventral horn. By 14 days bFGF LI was also observed in contralateral dorsal and ventral horns. In contrast, we found no obvious staining differences in lumbar spinal cord following the chronic constriction injury. This study demonstrated increased specific cytokine and growth factor-like expression in the spinal cord following peripheral nerve injuries. It also showed a differential expression of bFGF in two distinct mononeuropathy models. These results provide further evidence that central cytokine production via a neuroimmune cascade may be involved in the development and maintenance of behaviors that mimic neuropathic pain following nerve injury.     

Effect of synaptic adhesion-like molecule 3 on epileptic seizures: Evidence from animal models

Axonal sprouting and synaptic reorganization are the primary pathophysiological characteristics of epilepsy. Recent studies demonstrated that synaptic adhesion-like molecule 3 (SALM3) is highly expressed in the central nervous system and plays important roles in neurite outgrowth, branching, and axon guidance, mechanisms that are also observed in epilepsy. However, the expression of SALM3 in the epileptic brain and the effect of SALM3 in the pathogenesis of epilepsy remain unclear. The aims of this study were to investigate SALM3 expression in rat models of epilepsy and to explore the functional significance of SALM3 in epilepsy. We demonstrated that SALM3 was expressed at significantly higher levels in epileptic rats compared with controls. Inhibition of SALM3 by SALM3 shRNA inhibited status epilepticus in the acute stage of disease and decreased spontaneous recurrent seizures in the Lithium-pilocarpine model of chronic stages of epilepsy. Consistent with these findings, SALM3 shRNA significantly prolonged the latent period in the PTZ kindling model. Our study suggests that the overexpression of SALM3 might be associated with epileptogenesis and that selectively inhibiting SALM3 may have therapeutic potential in treating epilepsy.     

Melatonin in animal models

Melatonin is a hormone synthesized and secreted during the night by the pineal gland. Its production is mainly driven by the Orcadian clock, which, in mammals, is situated in the suprachiasmatic nucleus of the hypothalamus. The melatonin production and release displays characteristic daily (nocturnal) and seasonal patterns (changes in duration proportional to the length of the night) of secretion. These rhythms in circulating melatonin are strong synchronizers for the expression of numerous physiological processes. In mammals, the role of melatonin in the control of seasonality is well documented, and the sites and mechanisms of action involved are beginning to be identified. The exact role of the hormone in the diurnal (Orcadian) timing system remains to be determined. However, exogenous melatonin has been shown to affect the circadian clock. The molecular and cellular mechanisms involved in this well-characterized "chronobiotic" effect have also begun to be characterized. The circadian clock itself appears to be an important site for the entrapment effect of melatonin and the presence of melatonin receptors appears to be a prerequisite. A better understanding of such "chronobiotic" effects of melatonin will allow clarification of the role of endogenous melatonin in circadian organization.     

Genetic animal models: focus on schizophrenia

The neurobiology of schizophrenia remains poorly understood. Symptoms of schizophrenia are classically thought to be associated with an imbalance of the dopaminergic system. However, the contribution of other neurotransmitters, in particular glutamate, has been increasingly appreciated. The role of individual components of neurotransmitter systems in aberrant behaviors can be experimentally tested in transgenic animals. Dopamine transporter knockout mice display persistently elevated dopaminergic tone and therefore might be appropriate substrates to evaluate the dopamine hypothesis. Similarly, NMDA receptor-deficient mice can be used to evaluate the glutamate hypothesis of schizophrenia. In this review we discuss how such animal models might be relevant for understanding the neurochemical underpinnings of certain manifestations of schizophrenia.     

Behavioral animal models of depression

Depression is a chronic, recurring and potentially life-threatening illness that affects up to 20% of the population across the world. Despite its prevalence and considerable impact on human, little is known about its pathogenesis. One of the major reasons is the restricted availability of validated animal models due to the absence of consensus on the pathology and etiology of depression. Besides, some core symptoms such as depressed mood, feeling of worthlessness, and recurring thoughts of death or suicide, are impossible to be modeled on laboratory animals. Currently, the criteria for identifying animal models of depression rely on either of the 2 principles: actions of known antidepressants and responses to stress. This review mainly focuses on the most widely used animal models of depression, including learned helplessness, chronic mild stress, and social defeat paradigms. Also, the behavioral tests for screening antidepressants, such as forced swimming test and tail suspension test, are also discussed. The advantages and major drawbacks of each model are evaluated. In prospective, new techniques that will be beneficial for developing novel animal models or detecting depression are discussed.