动态关节松动术治疗颈型颈椎病患者的临床研究

目的探讨动态关节松动术治疗颈型颈椎病活动受限患者的临床疗效。方法选取2013年7月~2014年5月青岛市立医院东院运动医学中心的颈型颈椎病患者60例,随机分为治疗组(30例)和对照组(30例),治疗组采用动态关节松动术进行治疗,对照组应用常规非手术治疗,给予牵引治疗。并应用VAS评分表评估疗效。结果治疗前,治疗组与对照组在颈椎活动度(屈伸、旋转)和VAS评分方面差异无统计学意义(P0.05)。治疗5次后,两组颈椎活动度和VAS评分与治疗前比较,差异有统计学意义(P0.05)。与对照组相比,治疗组明显优于对照组,颈椎活动度(前屈、后伸、旋转)明显改善。结论动态关节松动术治疗颈型颈椎病可明显改善患者的疼痛,改善颈椎的活动度,且安全、经济,疗效明显。     

Learning, memory, and glial cell changes following recovery from chronic unpredictable stress

Previous research has indicated that chronic stress induces inflammatory responses, cognitive impairments, and changes in microglia and astrocytes. However, whether stress-induced changes following recovery are reversible is unclear. The present study examined the effects of chronic unpredictable stress (CUS) following recovery on spatial learning and memory impairments, changes in microglia and astrocytes, and interleukine-1β (IL-1β) and glial-derived neurotrophic factor (GDNF) levels. Mice were randomly divided into control, stress, and recovery groups, and CUS was applied to mice in the stress and recovery groups for 40 days. Following the application of CUS, the recovery group was allowed 40 days without stress. The results of the Morris water maze illustrated that CUS-induced spatial learning and memory impairments could be reversed or even improved by a period of recovery. Immunohistochemical tests revealed that CUS-induced alterations in microglia could dissipate with time in the CA3 region of the hippocampus and prelimbic areas. However, CUS-induced activation of astrocytes was sustained in the CA3 area following recovery. Western blot analyses revealed that CUS induced a significant increase of GDNF and a significant decrease in IL-1β. Additionally, increased GDNF levels were sustained in the hippocampus during recovery. In conclusion, this study provides evidence that CUS-induced learning and memory impairments could be reversible following recovery. However, activated astrocytes and increased GDNF levels in the hippocampus remained elevated after recovery, suggesting that activated astrocytes and increased GDNF play important roles in the adaptation of the brain to CUS and in repairing CUS-induced impairments during recovery.     

Effect of early life housing manipulation on baseline and drug-induced behavioural responses on neurochemistry in the male rat

Employing environmental enrichment (EE) provides continual sources of dynamic interaction for animals. Though an established discipline in behavioural science, the consequences of EE on behavioural pharmacological tests have not been extensively examined. The purpose of this study was to examine the consequences of EE (or isolation housing) on a range of behavioural pharmacological tests and brain monoamine and brain-derived neurotrophic factor (BDNF) expression in the rat. Male rats were randomly assigned to IC (isolation), SC (standard group-housed) or EE conditions. IC and SC animals were housed singly or in groups of four in standard cages, whilst the EE group were housed in groups of four in larger cages enriched with a variety of wooden, cardboard and plastic objects. After 5weeks of housing, its impact on the effects of diazepam (DZP) in the elevated plus maze (EPM); desipramine (DMI) in the forced swim test (FST) and amphetamine (AMP) effects on homecage activity were assessed. Post-mortem monoamine and BDNF levels were analysed using HPLC and ELISA. EE rats displayed reduced activity in the OFT, however no other differences were found in baseline behaviours. DMI reduced immobility time in the FST, but only for rats housed in IC, while AMP effects were somewhat greater for socially-housed animals than those in IC. There were no housing effects on monoamine or BDNF levels in discreet brain regions. The results suggest that post-weaning enrichment had no significant effect on baseline behaviours or monoamine and BDNF levels, thus it is suitable to implement as a commonplace husbandry practice, however, caution must be taken when investigating responsiveness to psychotropic drugs.     

Elucidating the role of 5-HT(1A) and 5-HT(7) receptors on 8-OH-DPAT-induced behavioral recovery after experimental traumatic brain injury

8-OH-DPAT is a 5-HT(1A/7) receptor agonist that enhances behavioral recovery after traumatic brain injury (TBI). This study is a first attempt to decipher whether the benefits induced by 8-OH-DPAT after TBI are mediated by 5-HT(1A) or 5-HT(7) receptors. A single i.p. injection of 8-OH-DPAT (0.5 mg/kg) alone or co-administered with either the 5-HT(1A) or 5-HT(7) receptor antagonists WAY 100635 (0.5 mg/kg) or SB 269970 HCl (2.0 mg/kg), respectively, or vehicle control (1.0 mL/kg) was given 15 min after cortical impact or sham injury. Function was assessed by established motor and cognitive tests. No difference in motor performance was observed among the TBI groups. Spatial acquisition was enhanced, relative to vehicle controls, by 8-OH-DPAT alone and when co-administered with WAY 100635, but not when combined with SB 269970 HCl. These data imply that 5-HT(1A) receptor antagonism does not abate the 8-OH-DPAT-induced cognitive benefits, but 5-HT(7) receptor antagonism does, which suggests that the 8-OH-DPAT-induced benefits in this single administration paradigm may be mediated more by 5-HT(7) versus 5-HT(1A) receptors. Evaluation of a specific 5-HT(7) receptor agonist will further elucidate the contribution of 5-HT(1A) and 5-HT(7) receptors on behavioral recovery conferred by acute 8-OH-DPAT treatment after TBI.     

Ladostigil prevents age-related glial activation and spatial memory deficits in rats

Oxidative stress and glial activation occur in the aging brain. Ladostigil is a new monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitor designed for the treatment of Alzheimer's disease. It has neuroprotective and antioxidant activities in cellular models at much lower concentrations than those inhibiting MAO or AChE. When ladostigil (1 mg/kg/day) was given for 6 months to 16-month-old rats it prevented the age-related increase in activated astrocytes and microglia in several hippocampal and white matter regions and increased proNGF immunoreactivity in the hippocampus towards the levels in young rats. Ladostigil also prevented the age-related reduction in cortical AChE activity and the increase in butyrylcholinesterase activity in the hippocampus, in association with the reduction in gliosis. The immunological and enzymatic changes in aged rats were associated with improved spatial memory. Ladostigil treatment had no effect on memory, glial or proNGF immunoreactivity in young rats. Early treatment with ladostigil could slow disease progression in conditions like Alzheimer's disease in which oxidative stress and inflammatory processes are present.     

Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory pathways in mice

Evidence suggests that obesity-induced cognitive impairments are driven by in brain inflammatory responses and inflammation-mediated brain insulin resistance. Ursolic acid (UA), a triterpenoid compound, has many important biological functions, including antioxidant and anti-inflammatory activities. Here, we evaluated the effect of UA on cognitive impairment induced by a high-fat diet (HFD), and we explored the potential mechanisms mediating this effect.Results showed that UA administration significantly improved the behavioral performance of C57/BL6J mice fed a HFD in both the step-through test and the Morris water maze task. These results were associated with the inhibition of endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory signaling and the restoration of insulin signaling and phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. UA administration also increased memory-related protein expression in the hippocampus of mice given a HFD. However, the neuroprotective effects of UA were blocked by an intracerebroventricular (i.c.v.) injection of PI-103, a specific PI3K 110α inhibitor.These results suggest that UA may be a potent candidate for the prevention and treatment of cognitive deficits caused by type 2 diabetes.     

IGF-I ameliorates hippocampal neurodegeneration and protects against cognitive deficits in an animal model of temporal lobe epilepsy

Epilepsy is a major neurological disease, and patients often show spatial memory deficits. Thus, there is a need of effective new therapeutic approaches. IGF-I has been shown to be neuroprotective following a number of experimental insults to the nervous system, and in a variety of animal models of neurodegenerative diseases. In the present work, we investigated the possible neuroprotective effects of IGF-I following unilateral intrahippocampal administration of kainic acid (KA), an animal model of temporal lobe epilepsy (TLE). KA induced cell death, as shown by FluoroJade B, and extensive cell loss in both the ipsilateral and contralateral CA3 and CA4 areas, as well as granule cell dispersal in the DG, as revealed by Cresyl violet staining. KA also resulted in intense astrogliosis and microgliosis, as assessed by the number of GFAP and CD11b immunopositive cells, respectively, and increased hippocampal neurogenesis. Exposure to the Morris Water Maze task revealed that mice injected with KA were deficient in spatial learning and both short- and long-term memories, when tested in a larger diameter pool, which requires the use of allocentric strategies. When tested in a smaller pool, only long-term memory was impaired. Administration of IGF-I decreased seizure severity, hippocampal neurogenesis, and protected against neurodegeneration at the cellular level as assessed by FluoroJade B and Cresyl violet staining, as well as the number of GFAP and CD11b immunopositive cells. Furthermore, IGF-I abolished the cognitive deficits. Our results support that IGF-I could have a possible therapeutic potential in TLE.     

多重脑震荡对大鼠空间认知行为的影响

目的探讨多重脑震荡（MCC）对大鼠认知行为的影响。方法成年SD大鼠24只，应用自制金属单摆式闭合性脑损伤机械打击装置复制MCC大鼠模型，随机分为对照组和MCC组，伤后应用Morris水迷宫实验，评价大鼠的空间学习记忆功能。结果在Morris水迷宫测试中，与对照组（8～14d测试结果分别为：64．74±23、43，33．16±17．70，36．59±27．53，37、60±18．20，37．14±26．03，16．85±10．63，10、02±6．51）相比，MCC大鼠伤后8～14d找到平台的时间明显延长，且在伤后的第9d（71．74±35．76）、第10d（63．14±31．02）、第13d（47．51±40．93）、第14d（42、39±43．33）差异具有显著性。在无平台探测实验中，与对照组（23．89±11．82）相比，MCC后第14d（15．12±6．56）大鼠在原有平台第三象限停留时间明显减少，差异显著（P〈0．05）。结论实验性多重脑震荡大鼠在Morris水迷宫实验中，出现较为严重的空间认知行为障碍。     

雄激素对SAMP8小鼠学习记忆能力及海马神经元的影响

目的探讨雄激素对SAMP8小鼠学习记忆能力及海马CA1区神经元的影响。方法7月龄雄性SAMP8小鼠30只,随机分为假手术组、去势组及去势 雄激素补充治疗组。十一酸睾酮(TU)剂量为37.4mg/(kg.15d)。雄激素补充治疗45d后,通过Morris水迷宫观察小鼠学习记忆能力;用苏木素伊红染色,Aβ免疫组织化学及图像分析观察海马CA1区神经元的变化。结果1.Morris水迷宫中,去势组定位航行试验潜伏期明显长于其他组(P<0.05),探索实验跨越平台次数减少(P<0.05)。TU补充治疗能改善学习记忆能力,与假手术组比较差异无统计学意义(P>0.05)。2.去势组海马CA1区弥漫性空泡变性,细胞排列疏松、紊乱,核深染、固缩;Aβ阳性神经元染色深,其数量及吸光度(A)明显高于其他组(P<0.05)。结论去势后,雄激素缺乏可导致学习记忆能力下降,海马神经元严重损伤,雄激素补充治疗可减轻神经元损伤,改善学习和记忆能力。     

Efficacy assessment of a combined anticholinergic and oxime treatment against topical sarin-induced miosis and visual impairment in rats

Background and Purpose

Eye exposure to the organophosphorus (OP) irreversible cholinesterase inhibitor sarin results in long-term miosis and impaired visual function. We have previously shown that tropicamide is better at ameliorating this insult than topical atropine or cyclopentolate. However, to minimize side effects associated with repeated tropicamide applications and high treatment doses, we evaluated the effects of oximes (ChE re-activators) alone and combined with tropicamide at ameliorating OP-induced ocular impairments.

Experimental approach

Rats were topically exposed to sarin, followed by topical treatment with various oximes alone or in combination with tropicamide. Pupil width and light reflex were measured by an infrared-based digital photograph system, while visual performance was assessed by employing the cueing version of the Morris water maze (MWM).

Key Results

Oxime treatment following sarin ocular exposure induced a slow persistent pupil widening with efficacy in the order of HLö-7 > HI-6 > obidoxime = TMB-4 = MMB-4. In the light reflex test, the ability of the iris to contract following oxime treatment was mostly impaired at 1 h and was back to normal at 4 h following sarin exposure. All oxime treatments ameliorated the sarin-induced visual impairment as tested in the visual task (MWM). The combined topical treatment of tropicamide with an oxime induced a rapid improvement in pupil widening, light reflex and visual performance, and enabled a reduction in tropicamide dose.

Conclusions and Implications

The use of tropicamide combined with an oxime should be considered as the topical treatment of choice against the toxic effects of ocular OP exposure.