伽玛刀低剂量照射对致疒间大鼠海马中氨基酸递质的影响

目的观察伽玛刀低剂量照射对致疒间大鼠海马中谷氨酸(Glu)、γ-氨基丁酸(GABA)的影响,探讨伽玛刀治疗癫疒间的作用机制。方法将50只锂-匹罗卡品致疒间大鼠随机分为照射组和非照射组,各25只,另取正常大鼠25只(腹腔注射生理盐水)作为对照组。照射组大鼠进行伽玛刀低剂量照射(周边剂量20Gy),对照组和非照射组大鼠不进行伽玛刀照射。用高效液相色谱-质谱-质谱(HPLC-MS-MS)分析法检测各组大鼠海马Glu、GABA的含量。结果伽玛刀照射2周后,照射组和非照射组大鼠海马中Glu含量均高于对照组,照射组GLu含量低于非照射组,差异具有统计学意义(P0.05);照射组和非照射组GABA含量均低于对照组,照射组GABA含量高于非照射组,差异具有统计学意义(P0.05)。结论伽玛刀低剂量照射通过调节海马中Glu与GABA的平衡,以达到抗癫疒间的作用。     

伽玛刀照射正常大鼠海马组织形态学结构的变化

目的研究伽玛刀照射对正常大鼠海马组织形态学结构的影响。方法利用自行设计的伽玛刀大鼠立体定位头架，分别应用剂量为20、40、60、80、100和150Gy的伽玛射线对大鼠海马组织进行照射。采用电镜观察照射后海马神经细胞超微形态结构变化，MRI观察影像学表现。结果电镜结果显示：100Gy和150Gy剂量引起海马神经细胞严重损伤，60Gy引起轻度损伤，在40Gy时胶质细胞和血管内皮细胞已有肿胀。100Gy照射后，1个月内大鼠靶区无影像学改变，3个月时大鼠靶区表现为高信号。结论海马组织的损伤程度与伽玛刀的照射强度存在剂量一效应关系和时间一效应关系，海马神经元比胶质细胞和血管内皮细胞更具放射耐受性。     

小剂量伽玛刀照射对致癎大鼠脑神经元nNOS表达的影响

目的 通过观察低剂量伽玛刀照射对致痫大鼠大脑皮质及海马神经元nNOS表达的影响，初步探讨伽玛刀治疗癫痫的作用机制。方法 将44只青霉素致痫大鼠模型等分为实验组和实验对照组，对实验组进行伽玛刀照射（周边剂量12Gy），应用免疫组化方法检测两组大脑皮质及海马神经元nNOS表达的变化。结果 nNOS在两组动物的皮质和海马表达均有显著性差别．实验组显著性低于实验对照组；实验对照组表达呈双高峰现象。结论 nNOS在伽玛刀治疗癫痫的机制中具有重要作用。     

伽玛刀照射猴三叉神经的病理组织学研究

目的 观察伽玛刀照射猴三叉神经的病理组织学变化,探讨伽玛刀治疗原发性三叉神经痛(TN)的放射生物学效应机制和照射神经长度-剂量的效应关系.方法 选择5只恒河猴,1只为对照,4只行伽玛刀照射,选择靶点为三叉神经根,一侧为单靶点照射,对侧为双靶点照射,给予剂量分别为60 Gy、70 Gy、80 Gy、100 Gy.照射后6个月取病理,行光镜、透射电镜及免疫组织化学检查.结果 在相同剂量照射下,单靶点照射与双靶点照射的神经组织结构损伤程度变化基本一致.60 Gy、70 Gy见少许神经纤维脱髓鞘,轴突变性、断裂或消失.80 Gy神经组织结构损伤程度加重.100 Gy神经组织结构损伤程度更重,可见部分神经坏死.结论 60 Gy、70 Gy对三叉神经的组织结构变化影响小,80 Gy可引起三叉神经部分轴突的变性、消失及脱髓鞘,更高的剂量(100 Gy)可导致部分神经坏死.单靶点照射与双靶点照射神经组织结构损伤程度相近,两者的照射神经长度-剂量效应关系差异无统计学意义.     

伽玛刀对癫痫大鼠模型的治疗作用及机制研究

目的 研究伽玛刀照射对癫痫大鼠的放射生物学作用,探讨伽玛刀治疗癫痫的作用机制.方法 制备海人酸大鼠癫痫模型,利用自行设计的伽玛刀动物定向头架,分别应用100Gy和20Gy的伽玛射线对癫痫大鼠海马组织进行照射,观察大鼠行为学、脑电图、MRI及超微结构、脑组织氨基酸含量及GABA能神经元表达变化.结果 伽玛刀照射后大鼠癫痫发作次数明显减少.100Gy组照射后2个月MRI表现为靶区高信号,20Gy组5个月MRI未见改变.伽玛刀照射后兴奋性氨基酸含量显著低于癫痫组,GABA能神经元表达低于正常,但高于癫痫组.结论 伽玛刀照射对癫痫大鼠具有治疗作用,高剂量伽玛射线(100Gy)对致痫灶有毁损作用.低剂量伽玛射线(20Gy)通过抑制兴奋性神经元释放兴奋性氨基酸使癫痫发作减少.     

伽玛刀对大鼠海马体内体外放射生物学作用

目的 探讨伽玛刀照射对大鼠海马组织与培养的海马神经元放射生物学作用的差异.方法 分别对大鼠海马组织和堵养的海马神经元进行伽玛刀照射,观察照射前后组织超微结构变化、FOS和HSP70表达以及细胞存活情况.结果 在体海马组织和培养的海马神经元对放射反应不同.高剂量(150和100Gy)引起在体海马组织严重损伤,60Gy引起轻度损伤,而低剂量(30Gy)即可引起培养的海马神经损伤和死亡.大鼠海马组织和培养的海马神经元的FOS和HSP70表达与照射强度和照射后时间有关.结论 海马组织和培养的海马神经细胞的损伤程度都与伽玛刀的照射强度存在明显的剂量-效应关系和时间-效应关系,但两者对伽玛射线的反应存在一定差异.     

半脑照射后早期海马神经元密度的研究

目的 :探讨半脑照射后大鼠的海马神经元密度变化规律。方法 :采用 4Mev的电子束对 8～ 10周龄的雌性SD大鼠作半脑照射 ,照射剂量分别为 5、15、3 0Gy。另设对照组 (只麻醉 ,不照射 )。于照射后第 3天 ,1、3个月分别计数海马CA2区神经元密度。结果 :照射后海马神经元密度呈下降趋势 ,3 0Gy照射组有统计学差异。结论 :半脑照射可使大鼠的海马神经元密度下降 ,海马神经元密度程度与照射剂量有关。     

伽玛刀照射猫视神经后视神经病理学变化研究

目的 探讨引起视神经病理学变化的最小射线剂量。方法 20只家猫随机分成5组，每组4只，1组作为对照组，其余4组分别接受10Gy、11Gy、12Gy、13Gy伽玛刀的照射，照射后5个月，取病理，分别进行光镜及透射电镜检查，重点观察其电镜下超微病理结构的变化。结果 10Gy组结构正常，11Gy组光镜下结构出现轻微的变化，电镜下超微病理结构出现部分线粒体肿胀。12Gy组光镜及电镜下神经组织结构紊乱，广泛变性。13Gy组神经组织结构严重紊乱，大部分髓鞘脱失、溶解，神经微丝疏松、溶解，线粒体普遍空泡化、溶解改变。结论 引起视神经病理学变化的射线剂量为11Gy，引起视神经病理学质变的最小射线剂量为12Gy，随着剂量的增加对视神经的损伤加重。     

伽玛刀照射正常脑组织引起的放射生物学变化

不同剂量伽玛刀照射猫的大脑皮层,照射后不同时期(1个月,3个月,半年,1年)分别观察其组织学变化。结果:160Gy,180Gy,200Gy伽玛刀术后1个月均引起脑组织坏死,200Gy产生的坏死灶较大;100Gy,70Gy3个月时未见组织坏死,1年时引起严重晚期反应;50Gy,40Gy引起晚期迟发放射反应;30Gy1年时仅局部细胞数量减少,20和10Gy无变化。30Gy可能是伽玛刀引起脑组织放射反应的阈剂量。     

低剂量伽玛刀照射对致大鼠皮质及海马神经元c-fos和nNOS表达的影响

目的 通过观察低剂量伽玛刀照射对致痫大鼠大脑皮质及海马神经元c—fos和脑型一氧化氮合酶（nNOS）表达的影响，探讨伽玛刀治疗癫痫的作用机制。方法将44只青霉素致痫大鼠模型等分为实验组和实验对照组大鼠各22只，另取4只正常大鼠作为正常对照组。实验组行伽玛刀照射（周边剂量12Gy）后，应用免疫组化方法，观察大脑皮质及海马神经元c-fos和nNOS表达的变化。结果无论是皮质还是海马，c—fos和nNOS在实验组与实验对照组动物之间，表达均有明显的差别，实验组表达明显少于实验对照组，而后者呈现双高峰现象。结论c—fos和nNOS在伽玛刀治疗癫痫的机制中发挥了重要作用。     

伽玛刀治疗视神经压迫垂体腺瘤的可行性研究

目的探讨伽玛刀治疗压迫视神经垂体腺瘤的可行性。方法采用LeksellB型伽玛刀对119例有视神经压迫的垂体腺瘤进行治疗，以40％～80％等剂量曲线包裹肿瘤，中心剂量30～80Gy，平均45.3Gy；边缘剂量15-35Gy．平均29．5Gy；视通路的接受剂量低于10Gy。100例获得随访。结果偏盲和视力改善率为80、0％，激素分泌控制率为82．5％，肿瘤生长控制率为98．0％。结论伽玛刀可作为有视神经压迫垂体腺瘤的备选治疗，在对视神经减压的同时能有效控制激素分泌和肿瘤生长。     

低剂量伽玛刀照射癫癎大鼠脑神经元的超微结构研究

目的探索伽玛刀治疗原发性癫的细胞学机理。方法建立大鼠皮质青霉素局灶性癫癎模型,将SD大鼠随机分为实验组、实验对照组和对照组。照射周边剂量12 Gy, 等剂量曲线为50%。分别于0.5 h~2个月后取靶区皮质及海马标本制备光镜、常规透射电镜样品。结果癫癎模型鼠可见较多凋亡神经元,而癫癎模型鼠经低剂量伽玛刀照射后同时程的神经元改变较轻微,凋亡细胞少见。结论凋亡参与了青霉素致癫癎发作后海马神经元的死亡过程,低剂量伽玛刀照射对抑制神经元的死亡过程有重要作用。     

大鼠正常脑组织伽玛刀照射后GFAP表达的实验研究

目的研究伽玛刀（Gamma knife）立体定向放射外科照射大鼠正常脑组织后亚急性期胶原纤维酸性蛋白（GFAP）的表达随时间的变化,探讨星形胶质细胞（AS）的增殖与放射损伤的关系。方法30只成年雌性Wistar大鼠,随机分为6组,每组5只。其中1组为假照射组,其余5组行伽玛刀照射。运用Leksell 23004B型伽玛刀4mm准直器以50Gy照射大鼠右侧尾壳核。不同组别的大鼠分别在照射后1、2、4、8、12周深度麻醉下断头取出脑组织,行免疫组织化学染色观察GFAP的表达。结果照射后4周靶区内GFAP阳性细胞数目开始增多,细胞形态变得不规则。至8周时GFAP阳性细胞进一步增多,胞体变大,胞浆染色较深。照射后12周GFAP阳性细胞数目最多,胞体明显肥大,形态各异,细胞突起粗大不规则,胞浆呈深棕色。结论伽玛刀放射外科以50Gy照射大鼠单侧尾壳核后,照射靶区GFAP阳性细胞数不断增加,细胞形态肥大、形状不规则。     

伽玛刀照射对猫视神经电生理学变化的影响

目的探讨不同剂量下伽玛射线照射后视神经电生理学的变化特点。方法20只猫随机分为5组,每组4只,1组作为对照,其余4组分别接受10Gy、11Gy、12Gy和13Gy伽玛刀的照射,分别于照射后3d、1周、半个月、1个月、2个月、3个月、4个月及5个月进行电生理监测。结果10Gy组电生理学没有变化,11Gy组在照射后1周出现了电生理学的变化,主要表现为潜伏期的延长,这种变化在半个月时有所恢复,随着时间的延长基本恢复正常。12Gy以上伽玛射线照射后出现了明显的电生理学异常变化,主要表现为潜伏期的延长和振幅的缩短,这种变化随着时间的延长而加重。结论引起视神经电生理学的变化特点与伽玛射线剂量有关,小剂量的伽玛射线可引起可逆性的变化,主要表现为潜伏期的延长。大剂量的伽玛射线可引起不可逆的视神经放射性损伤,这种损伤随着时间的延长逐渐加重,主要表现为潜伏期的延长和振幅的减小,随着时间的延长,振幅的减小更加明显。     

MR-based follow-up of the superior cerebellar artery after radiosurgery for trigeminal neuralgia

Purpose

To study with a non invasive method any potential radiological change on the superior cerebellar artery (SCA) in patients treated radiosurgically for classic trigeminal neuralgia (CTN).

Materials and methods

A retrospective measure of maximal dose received by SCA was performed analyzing the treatment planning in 55 consecutive patients treated by Gamma Knife radiosurgery for an CTN, then, a prospective study was designed using high resolution MR, with T2 SPIR, T1 without and with gadolinium enhancement, Proton density, 3D TONE and MIP reconstructions. Inclusion criteria were: patients followed at our institution, follow-up of one year or more, dose received by the SCA of 15 Gy or more and voluntary patient participation in the study. Patients with repeated Gamma Knife radiosurgery for failure or recurrence were excluded. The end points were: SCA occlusion, stenosis or infarction in the territory supplied by SCA.

Results

Sixteen patients were studied, with a mean follow-up of 25.2 months (12–42 months). The mean maximal dose received by the SCA was 57.5 Gy. (15–87 Gy). Among these 16 patients studied, neither obstruction of the SCA nor infarction was demonstrated. In one patient a suspicion of asymptomatic SCA stenosis was visualized distant to the irradiation field.

Conclusions

SCA can receive a high dose of irradiation during radiosurgical treatment for CTN. This study does not confirm any vascular damage to the SCA after radiosurgery for CTN.     

Gamma knife treatment of rat glioma——Influences of irradiation dose on apoptosis and necrosis

BACKGROUND： Apoptosis and necrosis are cellular death mechanisms that are induced in glioma cells following gamma knife irradiation. Increased apoptosis is essential for maintaining and enhancing treatment efficacy. OBJECTIVE： To observe apoptotic and necrotic mechanisms of rat glioma models induced by gamma knife treatment and to analyze the influences of irradiation doses on apoptosis and necrosis. DESIGN： Controlled animal experiment. SETTING： Cancer Hospital of Tianjin Medical University and Gamma Knife Center of Hefei Brain Hospital. MATERIALS： Eighteen female specific pathogen free Sprague Dawley rats, weighing 180 210 g and 5 6 weeks old, were purchased from the Experimental Animal Center, Medical College of Suzhou University. Rat C6 glioma cells were purchased from the cell bank of Chinese Academy of Sciences. Annexin V-FITC Reagent Kit （Bender Med System. Company, USA） and a flow cytometer （Becton Dickinson FACSCalibur） were provided. METHODS： The experiment was conducted at the Cancer Hospital of Tianjin Medical University and Gamma Knife Center of Hefei Brain Hospital from December 2006 to May 2007. All rats were inoculated with C6 glioma cells, i.e., 4 μL of a C6 glioma cell suspension was injected 5 mm deep in the cortex. All rats were divided randomly into a model group, 9-Gy treatment group, and 12-Gy treatment group. There were six rats in each group. MAIN OUTCOME MEASURES： Apoptosis and necrosis of normal brain tissue and glioma were observed by Flow Cytometry one week after irradiation, and pathological changes to tumor tissue were identified by HE staining. RESULTS： Eighteen rats were initially selected for the study： two rats from the model and 12-Gy treatment groups died from accidental anesthesia. The remaining 16 rats were included in the final result analysis. Cellular apoptosis and necrosis： apoptosis and necrosis were significantly increased in the treatment groups after gamma knife irradiation, compared to the model group （P 〈 0.05）. Apoptosis was grea     

颅咽管瘤的伽玛刀治疗

目的 探讨伽玛刀治疗颅咽管瘤的疗效、适应证及并发症。方法 自1993年11月至2000年12月,使用伽玛刀治疗实体颅咽管瘤86例。其中50例行立体定向穿刺囊性部分,44例进行同位素~(32)P内放疗。治疗病灶体积0.7～26.9cm~3,平均5.37cm~3。中心剂量19.6～30Gy,平均24.6Gy。边缘剂量9.8～14Gy,平均12.4Gy。视神经和视束受照剂量小于10Gy。采用45％～55％等剂量曲线。结果 79例获随访,随访10～88个月,平均随访47个月。实体肿瘤部分控制率为88.6％(70/79),囊性部分控制有效率79.3％(50/63)。结论 手术切除仍是颅咽管瘤的首选治疗方法。伽玛刀治疗实质性颅咽管瘤,安全且有效,是手术切除后肿瘤残留复发和颅咽管瘤囊腔内同位素内放疗后等治疗手段的重要补充。对于不愿接受手术或不能耐受手术切除的患者,伽玛刀治疗也是有效的治疗选择。     

Contralateral response of macrophages and astrocytes to injury in the cerebral hemisphere of 6-day-old rat following prenatal gamma irradiation.

Wistar pregnant rats were exposed to a single 1.0 Gy dose of gamma rays on gestational days 13, 15, 17 or 19 (E13, E15, E17 and E19, respectively). When offsprings of the irradiated females became 6-day-old, they received a mechanical injury of the cerebral hemisphere. One or 2 days after the injury, [3H]thymidine was injected and the animals were perfused. Brain sections were processed for BSI-B4 isolectin histochemistry or immunohistochemistry for glial fibrillary acidic protein (GFAP) or S-100-beta protein and subjected to autoradiography to visualise proliferating and non-proliferating macrophages or proliferating astrocytes. Significant changes in the contralateral response to injury related to the day of prenatal irradiation could be detected. The response was minimal following irradiations performed on E15 and E17. At those stages of prenatal development, the majority of cortical neurons with interhemispheric connections were formed. Therefore, irradiation-induced reduction of the neurons might minimise transfer of pathogenic stimuli to contralateral areas via degenerating nerve fibers. Consequently, the degree at which the contralateral glial response reflected reactive changes at the lesion site might also be minimal. Results of the present study do not show in detail mechanisms underlying the differences in the contralateral reactivity to injury. They, however, might be of importance to histopathological investigations using animal models of cerebral dysplasia.     

Long-term tumor control of benign intracranial tumors after Gamma Knife radiosurgery in 280 patients followed more than 5 years

The objective of the study was to assess the long-term radiological outcome of benign intracranial tumors (BIT) after Gamma Knife radiosurgery. We report the radiological outcome of 280 patients who underwent radiosurgical irradiation for BIT in a single center. Our series included 120 meningiomas, 139 vestibular schwannomas, 12 other schwannomas and 9 pituitary adenomas. Serial imaging studies were performed after irradiation for at least 5 years for all patients. The median tumor volume was 1.9 cc, and the median margin dose was 12 Gy. After a median follow-up of 6.8 years, the tumor control rate was 92.1 %: tumor decreased in 176 cases (62.9 %), remained unchanged in 82 lesions (29.3 %) and increased in 22 cases (7.9 %). The actuarial tumor control rate was 93.2 % at 5 years, 92.3 % at 7.5 years and 91.0 % at 10 years. No atypical or malignant transformation of irradiated tumors occured during the follow-up period. Gamma Knife radiosurgery provides a high rate of tumor control for BIT even in the medium to long-term.     

脑膜瘤伽玛刀治疗的剂量—容积效应初步研究

目的 :探讨脑膜瘤伽玛刀治疗中的剂量 容积效应与并发症之间的关系。方法 :应用Logistic综合方程分析边缘剂量 15Gy的容积 风险概率关系和风险概率为 3%的剂量 容积关系 ;并应用Logistic综合方程回顾性地分析了 37例脑膜瘤伽玛刀治疗的风险概率与并发症的关系。结果 :边缘剂量为 15Gy的容积 风险概率呈直线关系 ,风险概率为 3%的剂量 容积呈反变曲线关系。37例脑膜瘤伽玛刀治疗后 ,在平均 16 4个月的随访期内 ,3%警戒线以下 18例 ,无并发症发生 ,3%警戒线以上 19例 ,有 5例 ( 5 / 19,2 6 7% )发生并发症 (P <0 0 5 )。结论 :脑膜瘤伽玛刀治疗中的剂量的选择依赖于容积 ,按照容积大小分组选择剂量可以提高治疗的安全性 ,3%等效应线可以作为脑膜瘤伽玛刀治疗的警戒线。