内镜经鼻蝶手术治疗颅底脊索瘤

目的探讨内镜下经鼻蝶治疗颅底脊索瘤的技术、方法和手术指征。方法自2000年6月至2006年6月,应用神经内镜经鼻蝶入路手术治疗颅底脊索瘤30例。29例应用30°,70°硬性神经内镜,经鼻中隔和中鼻甲间入路,用高速磨钻磨除相应的骨性结构,显露肿瘤并分块切除。1例在显微外科下开颅切除颅内部分肿瘤,然后在神经内镜引导下,经鼻蝶切除斜坡、鞍区蝶筛窦、上颌窦、颞下窝的肿瘤。18例在术后6-12个月获得随访。结果肿瘤近全切除7例,次全切除16例,部分切除7例。24例术后获得一定程度上的临床症状和体征的改善,6例无变化。所有病人在术后7- 10d可恢复日常生活。1例在出院后20d因脑脊液漏再次入院做修补手术。随访的18例中,有4例在术后10-18个月复发,这4例均为广泛性生长的病例。结论内镜经鼻蝶手术治疗颅底脊索瘤有明显的优势。其操作简便安全;术中视野清楚,有利于显露;术后严重并发症少,病人恢复快,住院时间短。     

经蝶切除蝶骨斜坡区脊索瘤

目的 探讨颅底脊索瘤的手术入路和治疗方法，以提高肿瘤的全切率和治疗效果。方法 经蝶入路切除蝶骨斜坡区脊索瘤。结果 肿瘤次全切除14例（73．7％），大部分切除5例（26．3％）。14例大部分切除无死亡。5年生存率58％。结论 经蝶入路是一种安全，有效，创伤小，省时的手术入路；适宜切除大多数蝶骨斜坡区脊索瘤；积极切除肿瘤术后结合放疗可提高生存质量并能明显延长生存率。     

颅底脊索瘤的内镜经鼻手术治疗分型及入路

目的 探讨一种适合内镜经鼻手术治疗需要的颅底脊索瘤临床分型及入路选择方法.方法 回顾性分析2007年8月至2012年8月于我院使用内镜经鼻手术治疗的133例颅底脊索瘤病例资料.依据内镜经鼻手术斜坡解剖区域分类方法对脊索瘤进行临床分型.其中,主体位于颅底中线区域116例:(1)主体位于前颅底6例;(2)主体位于上斜坡7例;(3)主体位于上中斜坡42例;(4)主体位于中下斜坡8例;(5)主体位于下斜坡21例;(6)主体位于全斜坡32例.主体位于中线及中线旁区域(广泛型)17例.全部病人均行内镜经鼻手术切除.中线区域型共使用4种内镜经鼻手术入路:内镜经鼻-前颅底入路、内镜经鼻-上斜坡入路、内镜经鼻-中斜坡入路、内镜经鼻-下斜坡入路.广泛型使用内镜经鼻手术入路结合其他开颅手术入路进行肿瘤切除.结果 病变全切为26例(20％),次全切62例(47％),大部切除38例(29％),部分切除7例(5％).结论 制定适合内镜经鼻手术的斜坡解剖区域划分,并以此为基础对颅底脊索瘤进行临床分型,可以更好地指导内镜经鼻切除颅底脊索瘤的手术入路选择.     

经鼻蝶入路切除鞍区斜坡肿瘤

目的:探讨经鼻蝶入路切除鞍区斜坡肿瘤的优缺点。方法:经鼻蝶显微手术。结果:对118例鞍区斜坡肿瘤采用鼻蝶入路手术切除,效果满意,107例垂体腺瘤行全切或次全切除。3例囊性颅咽管瘤行永久性引流,6例脊索瘤行次全切除。结论:合理应用本手术入路,对某些颅底肿瘤的切除是一有效的途径。     

扩大额下硬膜外入路切除巨型斜坡脊索瘤(附13例报告)

目的　探讨巨型斜坡中线区脊索瘤的手术治疗方法。方法　采用经扩大额下硬膜外入路切除 13例巨型斜坡脊索瘤 (直径大于 4cm)。介绍入路方法、肿瘤切除程度和疗效随访 ,探讨肿瘤残留的原因和处理 ,并与其它入路比较适用范围。结果　本组巨型斜坡脊索瘤全切除 3例 ,次全或大部切除 7例 ,部分切除 3例 ,无手术死亡 ,无严重并发症。随访2～ 7年 ,3例肿瘤全切除者未见复发 ,其余 10例中 2例死亡 ,1例失访 ,3例病情稳定 ,另 4例因斜坡中线区以外肿瘤复发经其它入路再次手术 ,生存至今。结论　采用扩大额下硬膜外入路 ,切除主要沿颅底中线方向生长的巨型斜坡脊索瘤 ,疗效满意。对偏离中线方向生长的较大肿瘤 ,须采用联合入路手术。     

颞下经小脑幕锁孔入路解剖与临床应用

目的通过神经导航下颞下经小脑幕锁孔入路的解剖和手术方案研究,探讨该入路临床应用效果。方法应用成人头颅标本12例(24侧),模拟颞下经小脑幕锁孔入路,观察暴露的岩斜区解剖结构;利用神经导航技术定位标本岩骨内部结构,最大限度磨除岩尖,观察斜坡鞍后区,上、中斜坡区等结构;利用该入路切除11例临床颅底肿瘤,探讨该入路的安全性和实用性。结果颞下经小脑幕锁孔入路可完全暴露鞍旁区,通过海绵窦外侧壁的手术三角可对累及海绵窦内外病变进行直视手术;神经导航辅助下耳蜗、内听道等结构定位准确,头颅标本岩尖磨除后耳蜗内侧缘岩尖剩余最大骨质平均厚度(0.8±0.19)mm,内侧视角较非导航入路增加(8±2.5)°,后外侧视野增加了(25±3.2)°,获得(3.3±0.4)cm2硬膜显露,明显扩大了后颅窝的暴露范围。临床病例资料肿瘤全切除6例,次全切3例,大部分切除2例,手术时间与既往相比缩短1~1.5 h,术后新增脑神经损害症状或原有脑神经损害症状加重3例,无长期昏迷及手术相关死亡病例。结论神经导航辅助下颞下经小脑幕锁孔入路,能最大程度暴露蝶岩斜区病变,有利于提高肿瘤的全切率和术后疗效。     

导航下经蝶显微手术切除垂体微腺瘤

目的研究神经导航技术在经蝶显微切除垂体微腺瘤手术中的应用.方法在25例垂体微腺瘤经蝶手术中应用神经导航系统指导手术入路﹑肿瘤方位﹑切除范围.结果 25例垂体微腺瘤均达到镜下全切除,并通过术后MRI得到证实,且无严重手术并发症.结论在经蝶显微切除垂体微腺瘤手术中应用神经导航有利于全切病灶,降低手术并发症.     

经蝶入路颅底脊索瘤的显微手术治疗(附15例分析)

目的总结经蝶入路治疗颅底脊索瘤的手术经验。方法回顾性分析15例颅底脊索瘤病人的病例资料。肿瘤位于鞍区和中上斜坡13例,其中累及鞍内、鞍旁、蝶窦3例;呈侵袭性生长,累及中上斜坡和多组鼻窦2例。均采用经蝶窦入路手术。结果肿瘤全切除4例,次全切除8例,部分切除3例。术后临床症状得到不同程度改善11例,无明显缓解4例;无术后脑脊液漏、颅内感染等手术并发症发生,无死亡病例。部分切除病例中,术后12个月复发2例,术后2年复发伴远隔部位转移1例。结论对于局限于鞍区或中上斜坡及向鼻旁窦方向侵袭生长的颅底脊索瘤,经蝶窦入路可以很好地显露病变。该入路切除病变操作安全、省时,术后并发症少,病人恢复良好。     

神经内镜经颞下硬膜外锁孔入路治疗颅中窝肿瘤

目的总结经颞下硬膜外神经内镜锁孔入路手术切除颅中窝肿瘤的手术经验。方法回顾性分析5例颅中窝肿瘤的病例资料,均采用颞下硬膜外锁孔入路,在单纯内镜下切除肿瘤。结果肿瘤全切除4例,次全切除1例。术后病理为神经鞘瘤、间变型脑膜瘤、脊索样型脑膜瘤、脊索瘤和胆脂瘤。1例出现脑水肿,经甘露醇治疗后缓解。随访2～6个月,4例全切肿瘤无复发,1例脊索瘤稍进展行上颌部肿瘤切除术。结论经颞下硬膜外神经内镜锁孔入路手术切除颅中窝肿瘤,手术创伤小、术后并发症少,是切除颅中窝肿瘤安全有效的术式。     

神经导航辅助内镜下经鼻蝶入路手术治疗垂体腺瘤的疗效观察

目的 探讨神经导航辅助内镜下经鼻蝶入路切除垂体腺瘤的疗效。方法 2014年1月至2014年8月在神经导航系统引导下对49例垂体瘤患者行神经内镜下经单鼻孔蝶窦入路肿瘤切除术。术中实时导航定位相关解剖结构,内镜下切除肿瘤。术中均使用磨钻磨除骨质结构。术后随访1~6个月。结果 本组49例患者在导航辅助下均准确定位,术中未出现大血管及静脉窦损伤出血。肿瘤全切除35例（71.4%）,次全切除10例（20.4%）,大部分切除4例（2.2%）。术后绝大部分患者恢复良好,症状较术前明显改善,少数患者出现短期并发症。结论 内镜下经鼻蝶入路垂体瘤切除术中应用神经导航技术,有助于术中精确定位,快速而准确的找到病灶,减少局部重要结构的损伤,是一种安全、有效的手术方法。     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

经单侧鼻孔蝶窦入路切除垂体腺瘤(附60例报告)

目的 探讨经单侧鼻孔蝶窦入路手术治疗垂体腺瘤的手术方法及效果.方法 分析60例采用经单侧鼻孔鼻中隔蝶窦显微手术治疗垂体腺瘤的临床资料.结果 平均手术时间70 min,全切51例,大部分切除9例,因脑脊液鼻漏而行二次手术修补1例,颅内感染1例,无出血等并发症.结论 经单侧鼻孔蝶类入路显微手术是创伤小、安全、有效的垂体腺瘤切除方法.     

高血压脑出血的显微外科治疗进展

高血压脑出血（Hypertensive intrac-rebral hemorrhage,HICH）是具有高发病率、高病死率、高致残率的急性脑血管疾病,占所有脑卒中患者的10%-20%,早期病死率可高达49.4%。随着人口老龄化,其发病率逐年提高;而外科手术的干预,使其病死率有所下降,但致残率居高不下。如何提高手术疗效和患者生存质量,一直是神经外科医师努力的方向。微侵袭血肿清除术因其手术创伤小,恢复快,是目前国内治疗高血压脑出血的重要手段。     

神经内镜联合亚低温治疗高血压基底节区脑出血

目的 探讨神经内镜联合亚低温在治疗高血压基底节区脑出血中的临床应用价值.方法 回顾性分析我院神经内镜治疗高血压基底节区脑出血患者40例的临床资料,并对治疗结果进行分析.结果 神经内镜治疗组22例(甲组),神经内镜联合亚低温治疗组18例(乙组),术后3个月根据GCS评分,甲组恢复良好1例,中残4例,重残6例,植物生存6例,死亡5例;乙组恢复良好4例,中残8例,重残3例,植物生存1例,死亡2例,两组比较差异有统计学意义(P＜0.05).两组颅内压比较第1天两者差异不明显,但第2、3天亚低温组颅内压明显降低.结论 神经内镜是治疗高血压基底节区脑出血较为有效的手术方式,联合亚低温治疗能有效降低颅内压,改善术后神经功能恢复,具有较好的临床应用价值.     

Dysfunctional autophagy in Alzheimer＇s disease： pathogenic roles and therapeutic implications

Neuronal autophagy is essential for neuronal survival and the maintenance of neuronal homeostasis. Increasing evidence has implicated autophagic dysfunction in the pathogenesis of Alzheimer＇s disease （AD）. The mechanisms underlying autophagic failure in AD involve several steps, from autophagosome formation to degradation. The effect of modulating autophagy is context-dependent. Stimulation of autophagy is not always beneficial. During the implementation of therapies that modulate autophagy, the nature of the autophagic defect, the timing of intervention, and the optimal level and duration of modulation should be fully considered.     

Oxidative stress in Alzheimer＇s disease

Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons （lipids, proteins, and nucleic acids） can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid （Aβ） peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.     

Targeting 13-secretase with RNAi in neural stem cells for Alzheimer＇s disease therapy

There are several major pathological changes in Alzheimer＇s disease, including apoptosis of cho- linergic neurons, overactivity or overexpression of 13-site amyloid precursor protein cleaving enzyme 1 （BACE1） and inflammation. In this study, we synthesized a 19-nt oligonucleotide targeting BACE1, the key enzyme in amyloid beta protein （AI3） production, and introduced it into the pSilenCircle vector to construct a short hairpin （shRNA） expression plasmid against the BACE1 gene. We transfected this vector into C17.2 neural stem cells and primary neural stem cells, resulting in downregulation of the BACE1 gene, which in turn induced a considerable reduction in reducing AI3 protein production. We anticipate that this technique combining cell transplantation and gene ther- apy will open up novel therapeutic avenues for Alzheimer＇s disease, particularly because it can be used to simultaneously target several pathogenetic changes in the disease.     

Total saponins of Panax ginseng effects on proliferation and differentiation of human embryonic neural stem cells and in a Parkinson’s disease mouse model

BACKGROUND： Total saponins of Panax ginseng （TSPG） exhibits neuroprotection against Parkinson＇s disease in the substantia nigra. OBJECTIVE： To investigate the effects of TSPG on human embryonic neural stem cells （NSCs） proliferation and differentiation into dopaminergic neurons using in vitro studies, and to observe NSC differentiation in a mouse model of Parkinson＇s disease, as well as behavioral changes before and after transplantation. DESIGN, TIME AND SETTING： In vitro neural cell biology trial and in vivo randomized, controlled animal trial were performed at the Institute of Basic Medical Sciences, Chongqing Medical University between September 2004 and December 2007. MATERIALS： TSPG （purity 〉 95%） was isolated, extracted, and identified by Chongqing Academy of Chinese Materia Medica. Recombinant human basic fibroblast growth factor （bFGF） and recombinant human epidermal growth factor （EGF） were purchased from PeproTech, USA. A total of 25 C57/BL6J mice, aged 18-20 weeks were included. Twenty were used to establish a Parkinson＇s disease model with i.p. injection of MPTP （1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine） and TSPG alone or combined with interleukin-1 （IL-1）-treated NSCs prior to transplantation into the corpus striatum. The remaining five mice were pretreated for 3 days with TSPG prior to MPTP injection, serving as the TSPG prevention group. METHODS： Primary NSCs were isolated, cultured and purified from embryonic cerebral cortex. Immunocytochemistry was employed to detect specific antigen expression in the NSCs. In vitro experiment： （1） to induce proliferation, NSCs were treated with TSPG, EGF＋bFGF, or TSPG＋EGF＋bFGF, respectively; （2） to induce dopaminergic neuronal differentiation, NSCs were treated with TSPG, IL-1, or TSPG＋IL-1, respectively. MAIN OUTCOME MEASURES： In vitro experiment： the effects of TSPG on NSCs proliferation were evaluated with flow cytometry and MTT assay. Tyrosine hydroxylase expression was determined by immunocytochemistry assay to observe effects of TSPG on dopaminergic neuronal differentiation. In vivo experiment： differentiation of grafted NSCs in the mouse brain was determined by immunohistochemical staining. Behavioral changes were evaluated by spontaneous activity frequency, memory function, and score of paralysis agitans. RESULTS： （1） NSCs were cultured and passaged for more than three passages. Immunocytochemistry revealed positive nestin staining, as well as neurofilament protein and glial fibrillary acidic protein. （2） TSPG significantly increased NSC proliferation, in particular when combined with EGF and bFGF, which was twice as effective as FGF or bFGF alone. TSPG also induced dopaminergic differentiation in NSCs, in particular when TSPG was added together with IL-1, resulting in an effect five times greater than that of IL-1 alone. （3） At day 30 following transplantation, most NSCs in the TSPG prevention group differentiated into dopaminergic neurons, and the scores of paralysis agitans, spontaneous activity, and memory function were significantly increased compared with TSPG alone or TSPG＋IL-1 groups （P 〈 0.05）. CONCLUSION： TSPG stimulated NSC proliferation, in particular when combined with FGF and bFGF. TSPG significantly induced dopaminergic neuronal differentiation of NSCs, and the effect was greater when combined with IL-1. In addition, TSPG greatly improved behavior in the Parkinson＇s disease mouse model following NSC transplantation. Following NSC transplantation, TSPG pretreatment exhibited superior efficacy over either TSPG alone or TSPG in combination with IL-1, in terms of behavioral improvements in the Parkinson＇s disease mouse model.     

Edema and neuronal apoptosis in the hippocampus and cortex of elderly rats following transient cerebral ischemia/reperfusion injury

BACKGROUND： Previous studies of cerebral ischemia have used young animals, with an ischemic time greater than 5 minutes （safe time limit）. Despite an increased understanding of neuronal apoptosis, it remains uncertain whether brief cerebral ischemic events of 5 minutes or less damage brain tissue in elderly rodents. OBJECTIVE： To investigate the effects of transient cerebral ischemia （5 minutes）/reperfusion injury on brain cortical and hippocampal edema, aquaporin-4 （AQP-4） expression, and neuronal apoptosis in aged rats, and to compare ischemic sensitivity between cortex and hippocampus. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical School from April 2008 to March 2009. MATERIALS： Rabbit anti-AQP-4 polyclonal antibody, TUNEL kit, and SABC immunohistochemistry kit were purchased from Wuhan Boster Bioengineering, China. METHODS： A total of 160 healthy, male, aged 19-21 months, Wistar rats were randomly assigned to 4 groups： sham-surgery, and ischemia 1-, 3-, and 5-minute groups, with 40 rats in each group. The global cerebral ischemia model was established using the Pusinelli four-vessel occlusion, and the three cerebral ischemia groups were subdivided into reperfusion 12-hour, 1-, 2-, 3-, and 7-day subgroups, with 8 rats in each subgroup. The sham-surgery group was subjected to exposure of the first cervical bilateral alar foramina and bilateral common carotid arteries. MAIN OUTCOME MEASURES： The dry-wet weight assay was used to measure brain water content and histopathology of the cortex and hippocampus was observed following hematoxylin-eosin staining. In addition, cortical and hippocampal AQP-4 expression was detected by streptavidin-biotin complex immunohistochemistry, and neuronal apoptosis was detected by the TUNEL method. RESULTS： There was no significant difference in brain water content or AQP-4 expression in the cortex and hippocampus between ischemia 1- and 3-minute groups and the sham-surgery group or brain water content or AQP-4 expression in the cortex between ischemia 5-minute group and sham-surgery group （P 〉 0.05）. However, brain water content and AQP-4 expression in the hippocampus after 5 minutes of cerebral ischemia were significantly increased compared with the sham-surgery group （P 〈 0.05 or P 〈 0.01）. Several TUNEL-positive cells were observed in the cortex and hippocampus of the sham-surgery group and ischemia 1-minute group, as well as in the cortex of the ischemia 3-minute group. In addition, the number of apoptotic neurons in the hippocampus of ischemia 3-minute group and in the cortex and hippocampus of ischemia 5-minute group was significantly increased （P 〈 0.05 or P 〈 0.01 ）. Neuronal apoptosis was increased after 12 hours of ischemia/reperfusion, and it reached a peak by 2 days （P 〈 0.01）. CONCLUSION： Transient cerebral ischemia （5 minutes） resulted in increased hippocampal edema, AQP-4 expression, and neuronal apoptosis. Moreover, cerebral ischemia had a greater effect on neuronal apoptosis than brain edema or AQP-4 expression, and the hippocampus was more sensitive than the cortex.