胚胎中脑黑质脑内移植治疗帕金森病6例随访观察

本报告采用胚胎中脑黑质细胞脑内移植治疗6例晚期帕金森病，包括1例脑立件定向丘脑毁损后震颤复发，经移植治疗后获得良好效果。本组病例韦氏计分平均从21分降至11分。其中2例经术后3、9，14个月CT、MRI随访，脑内移植物体积增大．症状和体征明显改善。     

胎儿肾上腺髓质脑内移植术临床应用研究

本研究自1986年应用同种异体胎儿肾上腺髓质脑内纹状体移植,治疗重症震颤麻痹7例。术后随访长达二年半,5例显著进步,2例进步;术后半年内症状改善明显,脑脊液中多巴胺代谢产物—高香草酸(HVA)明显增高(P<0.001)。胎儿肾上腺髓质脑内移植治疗重症帕金森病有临床意义和推广价值。     

脑出血大鼠脑内神经干细胞移植的研究

目的分离并克隆新生大鼠神经干细胞,研究其移植入脑出血大鼠脑内的生物学特征,了解神经干细胞移植治疗脑出血的可行性.方法用尾状核注射Ⅶ型胶原酶制作脑出血模型,从Wistar新生大鼠脑室下区分离并克隆神经干细胞,经Brdu(5-溴脱氧尿嘧啶)掺入标记后移植入脑出血同侧的侧脑室或脑出血对侧的尾状核中.经免疫组织化学鉴定了解移植细胞在大鼠脑内的生存、迁移及分化情况.结果将稳定培养的神经干细胞移植入脑出血大鼠脑内,发现移植后4 d移植细胞仍存在.侧脑室移植组中移植细胞多在侧脑室周边区存在,尾状核移植组可见移植细胞开始向对侧迁移.免疫荧光双标证实细胞大多分化成神经元,少部分分化成胶质细胞.结论神经干细胞移植入脑出血大鼠脑内后能够存活,并能有效地穿过室管膜和向脑出血部位迁移.移植细胞在脑内大部分分化成神经元,少部分分化成胶质细胞.     

骨髓基质细胞移植治疗脑损伤研究进展

实验研究已证明骨髓基质细胞(MSCs)可以分化成多种神经细胞，脑实质内直接注射、脑脊液内注射或血管内注射移植后能促进脑损伤修复。血脑屏障的通透性可影响移植细胞进入脑内。MSCs移植的作用机制主要为替代受损细胞和产生内源性因子两种途径。对移植治疗效果的评估可能受到一些因素的影响。虽然仍存在一些尚待解决的问题．但MSCs移植治疗脑损伤是一种很有前途的治疗方法。     

颈上交感神经节的脑内移植—介绍一种新的巴金森氏病治疗方法

近年来脑组织移植治疗巴金森氏病使用的是胎儿脑,因排异反应、伦理方面等问题还远远不能适应于临床需要.作者通过自体周围神经节脑内移植来补充脑内多巴胺神经元.本研究通过动物的颈上交感神经节的脑内移植,以探讨治疗巴金森氏病的新方法.方法和结果1.大脑皮质内颈上交感神经的移植用40只大白鼠,全麻下摘出颈上交感神经节,制成2～3块细片,用一细的吸管将颈上交感神经节的细片移植到大脑皮质内,3周后用儿茶酚胺组织荧光法观察移植部位.再用20只大白鼠,移植前7天,在预定移植的大脑皮质内注入6羟基多巴(6-OHDA).移植3周后,移植片中可见许多大型细胞和小型细胞,且从这些细胞伸出许多儿茶酚胺神经纤维,但这些神经纤维几乎未到达脑实质内.移植片在移植前经6羟基多巴处理后,则可见从移植片发出的纤维束伸入脑内.2.甲苯四氢吡啶(MP-TP)致巴金森氏病的颈上交感神经节移植5只日本猴注射MPTP制成巴金森氏病模型,可见纹状     

超顺磁氧化铁标记骨髓基质干细胞移植治疗帕金森病鼠的实验研究

目的:研究应用超顺磁氧化铁(SPIO)标记骨髓基质干细胞(MSCs)移植治疗帕金森病(PD)大鼠后的在体MRI观察。方法:分离、获取大鼠骨髓基质细胞,脂质体转染法将SPIO标记MSCs;制作PD模型,SPIO标记的MSCs移植到PD大鼠右侧纹状体区,应用MRI在体观察脑内移植的骨髓基质细胞的存活和迁徙情况。结果:体外SPIO标记的骨髓基质细胞普鲁蓝染色阳性;脑内移植SPIO标记MSCs的PD大鼠磁共振T2和T2GRE扫描检查显示在移植区呈低信号改变。随时间的延长,移植区信号向周围扩大。脑纹状体区的铁染色也可见SPIO标记MSCs从移植部位向四周迁移。结论:SPIO可用于体外标记MSCs,通过MRI技术可以对标记细胞脑内移植后进行初步的活体示踪,有利于MSCs移植治疗PD后的疗效观察。     

前循环破裂动脉瘤伴脑内血肿的 早期显微手术治疗

目的 探讨早期显微手术治疗前循环破裂动脉瘤伴脑内血肿的疗效。方法 2010年12月至2013年12月显微手术前循环破裂动脉瘤伴脑内血肿26例,均发病后3 d内手术,采用翼点入路或扩大翼点入路23例,经额纵裂入路3例。结果 术后随访3个月至2年,GOS评分5分11例,4分9例,3分4例,2分1例,1分1例;术后DSA或CTA复查动脉瘤夹闭满意,载瘤血管通畅。结论 对前循环破裂动脉瘤伴脑内血肿,早期显微手术清除血肿并夹闭动脉瘤能够取得较为满意的临床效果。     

早期分化的神经干细胞移植治疗大鼠脑梗死的实验研究

目的研究早期分化的神经干细胞移植治疗脑梗死的可能性。方法从Wistar新生大鼠的大脑分离培养神经干细胞,取传代的神经干细胞诱导分化并经BrdU(5-溴脱氧尿嘧啶)标记后移植到脑梗死对侧的侧脑室,移植后对大鼠的功能恢复进行评价,用免疫组织化学方法鉴定移植的细胞在脑内的迁移和分化情况。结果将早期分化的神经干细胞移植到鼠脑后2周在梗死灶对侧可发现移植的细胞,4周时移植的细胞在梗死灶内分化为神经细胞,大鼠的学习功能和神经功能恢复较对照组均有明显改善。结论早期分化的神经干细胞移植到大鼠脑内仍能存活,并能有效穿过脑脊液———脑屏障迁移到脑梗死的部位;且分化为神经细胞。     

胚胎组织脑内移植治疗帕金森氏病临床CT和MRI随访观察报告

动物实验已证实,胚胎未成熟神经元脑内移植后,可以在宿主脑内存活、生长和建立新的神经突触联系,并可替代受损和变性的神经组织,有助于恢复中枢神经系统的功能和神经内分泌功能。但脑内移植物是否存活生长?尚缺乏影像学和组织学证据。本文报告1例接受人体胚胎组织脑内移植的患者,     

人脐血干细胞移植治疗大鼠脑缺血的实验研究

目的研究人脐血干细胞(HUCBCs)移植治疗脑缺血大鼠的疗效及HUCBCs在缺血大鼠脑内的状况。方法采集足月新生儿脐带血60～100ml,分离出其中的单个核细胞,体外培养并予5溴脱氧嘧啶尿苷(Brdu)标记48h。采用线栓法制作大鼠脑缺血再灌注模型,1d后将3×106HUCBCs经缺血侧侧脑室注射入大鼠脑内。在移植后不同时间对大鼠进行神经损害严重程度评分(NSS),用免疫组化技术观察移植后的HUCBCs的存活、迁徙、分化状况。结果HUCBCs在体外具有增殖能力;移植组大鼠自移植后3周起其NSS显著低于对照组(均P<0.05);移植后2周、4周、6周脑组织切片中均可见Brdu染色阳性细胞,缺血侧明显多于对侧(均P<0.05),移植后4周、6周明显多于移植后2周(均P<0.05);移植组各时间点脑组织切片中均可见神经巢蛋白阳性细胞;植入的HUCBCs在大鼠脑内能向损伤区域迁徙并能分化为星形胶质细胞、少突胶质细胞和神经元。结论HUCBCs能在缺血大鼠脑内存活、迁徙和分化,并能改善其神经功能。HUCBCs移植可作为脑梗死的有效治疗手段。     

脑外伤后进展性出血性脑损伤的诊治体会

目的研究脑外伤后进展性出血性脑损伤的临床特点,总结其发病机制,探讨及时诊断、治疗的方法。 方法回顾性分析解放军第二五一医院神经外科自2015年1月至2017年6月收治的167例脑外伤后进展性出血性脑损伤患者的临床资料。本组患者入院时按GCS评分：3~5分11例,6~8分36例,9~12分83例,13~15分37例。临床表现均有不同程度的颅高压症状,观察治疗过程中,76例患者出现意识障碍或意识障碍加深,94例患者肢体肌力减退,81例患者频繁呕吐,43例患者躁动,5例患者脑疝。 结果手术治疗94例,保守治疗73例。所有患者依据GOS评分判断：恢复良好114例,中残32例,重残13例,死亡8例（4.8%）。 结论动态CT观察是早期发现进展性出血性脑损伤的有效方法。对外伤性颅内血肿的患者绝不能仅仅依赖首次CT结果即制定一成不变的治疗方案,应进行专科监测和动态CT观察,根据患者血肿量的变化及时调整治疗方案。     

Efficacy and side-effects of long term L-dopa therapy in Parkinsonian syndromes (evaluated by CT scan as well) (author's transl)]

The evolution of symptoms and therapeutic response in a group of have been followed parkinsonian patients 81 for a period of 4 years. Hoehn and Yahr, and Webster's scales have been used. In addition CT scan, EEG, ECG, blood and urine analyses have been carried out. Treatment was carried out with L-Dopa and decarboxylase inhibitor (benserazide for 50% of cases and carbidopa for the other 50%). Anticholinergics (esp. metixene) were often required. The initial response was satisfactory for all patients except one who had hydrocephalus (with normal pressure). Four years later, the initial improvement diminished by about 1/3. Side effects occurred in 80.24% of cases in the beginning, and in 82.50% of cases after 4 years. Dyskinesias, confusional state and "on-off" phenomenon increased with time, whereas gastric trouble diminished. CT scan were obtained in all patients and atrophic changes were found in 82.7%. There were no correlations between localization and severity of anatomical lesions on the one hand, and therapeutic response and side-effects on the other. It is suggested that the severity of the disease depends mainly on the degree of neurochemical integrity in the affected area rather then to the extent of anatomical lesions.     

Diagnosis of congenital hydrocephalus and delivery of its patients in Japan

The study population included 193 patients with prenatally diagnosed (fetal) hydrocephalus and 181 with postnatally (12 or less than 12 months after birth) diagnosed (infantile) hydrocephalus identified by a nationwide questionnaire survey of congenital hydrocephalus performed in 2000. Of 180 patients with fetal, 101 (56.1%) were diagnosed before week 32 of gestation and 18 (10%) were diagnosed week 37 and later of gestation. In patients with fetal hydrocephalus, US was used in more than 80% of the cases, whereas in patients with infantile hydrocephalus, CT was used in more than half of the cases. For diagnosis of fetal hydrocephalus, either US or MRI had become dominantly utilized and CT had gone out of use in 1996–2000. The adoption ratio of cesarean delivery to transvaginal delivery was around 7 to 3 in patients with fetal hydrocephalus, and 2 to 7 in patients with infantile hydrocephalus, respectively, with significant difference between fetal hydrocephalus and infantile hydrocephalus groups (p < 0.001). Clinical outcomes in patients with fetal hydrocephalus was better in those delivered transvaginally than in those by cesarean delivery, although without no statistical significance (p = 0.124) and those in patients with infantile hydrocephalus showed almost no difference between transvaginal and cesarean delivery groups. There was a tendency for the Apgar score at 5 min to be lower in smaller birth weight infants with a body weight of less than 2000 g. This score could be useful as an index for predicting immediate postnatal death in patients with fetal hydrocephalus.     

Blood-brain barrier permeability is not altered by allograft or xenograft fetal neural cell suspension grafts.

Alterations in blood-brain barrier (BBB) function after brain grafting seem dependent on the donor phenotype and possibly on the grafting technique. Intracerebral blood grafts of nonneural tissue permanently disrupt the host BBB, while fetal neural block grafts probably do not. Cell suspensions, an alternative technique in brain grafting, disrupt the extracellular matrix of the graft. Fetal cell suspension allografts appear to form a functional BBB. We confirm and extend this finding to include fetal neural xenografts. Allograft and xenograft fetal neural cell suspensions were intracerebrally injected, and the BBB was examined using intravenous horseradish peroxidase (HRP). Neither graft type showed disruption of the BBB at the graft site from 2 weeks to more than 6 months after grafting. Vascular supply was prominent at all time points. Xenograft survival was improved with cyclosporine, yet cyclosporine did not affect BBB permeability. Cyclosporine did not interfere with repair of the BBB after simple brain trauma was induced by a control injection of saline. We conclude that fetal allograft and xenograft neural cell suspensions rapidly form and maintain a BBB impermeable to intravenous HRP.     

Oxygen transport in intraspinal fetal grafts: graft-host relations

In the present experiments, we determined tissue oxygen tension (PtO2) levels within the injured spinal cords of adult rats following transplantation of fetal spinal cord tissue. Partial resection cavities were made at L1-L2 levels after which whole pieces of 14-day donor tissue were placed into the cavities. Analysis of recordings obtained from graft tissues at 1 and 2 months after transplantation revealed low PtO2 values in many cases. Even the more extensively developed transplants at 3 months continued to show mean PtO2 levels lower than those taken from normal, mature spinal cord tissue. Measurements from host tissue, adjacent to a lesion in which no graft was introduced, showed normal or elevated PtO2 levels. In contrast, where extensive host and graft integration had occurred, the PtO2 levels of adjacent host resembled those obtained within the transplants. On the other hand, in cases of poor host-graft integration, characterized by either cellular or fibrotic graft-host interfaces or large cysts, the PtO2 tensions exceeded normal levels. Therefore, the present results show that when fetal grafts are placed acutely into an aspiration cavity within the adult spinal cord, the transplants quickly establish an oxygen microenvironment resembling that found during normal fetal development. Oxygen transport is therefore a regulated variable in the graft neuropil as it is in the normally developing spinal cord. Furthermore, in the presence of closely approximated fetal transplants, adjacent host tissue assumes tissue oxygen levels that mimic those in the graft. This "inductive" effect gradually diminishes as development proceeds and may be the hallmark of successful graft-host integration.     

术前栓塞联合显微手术治疗后颅窝实性血管母细胞瘤的疗效分析

目的探讨术前栓塞肿瘤供血动脉联合显微手术治疗后颅窝实性血管母细胞瘤的临床疗效。方法回顾性分析2012年5月至2018年7月郑州大学附属肿瘤医院神经外科收治的13例后颅窝实性血管母细胞瘤患者的临床资料。所有患者开颅手术前72 h内均予肿瘤供血动脉栓塞,术后予伽玛刀治疗。总结术前栓塞和显微手术的技巧,并分析手术疗效。患者入院、出院时采用Karnoisky功能状态评分(KPS)评估患者的生命质量。结果开颅术前肿瘤的栓塞程度>80%者4例,60%~80%者8例,<60%者1例。1例患者栓塞术后行MRI检查可见脑干局部梗死,临床表现为中枢性面瘫、吞咽困难加重。13例患者中,肿瘤全切除11例,次全切除2例。术中出血量为(620±35)ml,手术时间为(6.5±1.1)h。13例患者术前的颅高压症状均于术后明显缓解。术后新发吞咽功能障碍2例,听力减退1例,新发中枢性面瘫1例。13例患者出院时的KPS为(85.8±4.9)分,较入院时[(76.6±11.3)分]有明显改善(t=3.969,P=0.002)。所有患者均获随访,随访时间为6个月至3年(中位随访时间为22.6个月),末次随访的KPS为(88.1±3.6)分,与出院时比较差异无统计学意义(t=2.065,P=0.062)。仅1例次全切除患者于术后9个月肿瘤增大,再次给予伽玛刀治疗后未进展;其余12例肿瘤均无复发。2例患者发生梗阻性脑积水,予以脑室-腹腔分流术治疗后症状缓解。结论对于后颅窝实性血管母细胞瘤,术前行肿瘤供血动脉的栓塞能有效减少术中出血,甚至可达到分块切除肿瘤,从而降低了手术风险,有助于提高手术效果。     

腹腔镜辅助置管在脑室-腹腔分流术中的应用效果

目的探讨腹腔镜辅助放置分流管腹腔端在脑室-腹腔分流术中的应用效果。方法回顾性分析2018年5月至2019年11月北京大学第三医院神经外科收治的32例脑积水患者的临床资料。所有患者均采用脑室-腹腔分流术治疗,术中行腹腔镜辅助放置分流管腹腔端。临床随访结果以Salmon标准和Karnofsky功能状态评分(KPS)评估;同时行影像学随访,采用Evans指数评估脑积水的变化情况。结果32例患者在腹腔镜辅助下均顺利完成脑室-腹腔分流术,手术时间为(70.1±2.9)min(65~75 min),其中腹腔端操作时间为(16.1±1.5)min(14~20 min);术后住院时间为6~9 d(中位时间为7 d),其中卧床时间为2~3 d(中位时间为2 d)。无一例发生颅内感染、脑脊液漏、腹腔脏器损伤、分流管堵塞或死亡。1例出现呃逆症状,对症保守治疗后症状消失。术后随访(12.2±6.1)个月(3~22个月),按Salmon标准,3级2例(6.3%),2级18例(56.2%),1级12例(37.5%);32例患者的KPS由术前的(59.1±10.0)分(40~80分)增至(77.5±10.8)分(50~100分),差异有统计学意义(t=-13.826,P<0.001);Evans指数[中位数(四分位间距)]由术前的0.36(0.02)降至0.29(0.04),差异亦有统计学意义(Z=-4.961,P<0.001)。结论腹腔镜辅助脑室-腹腔分流术具有微创、精准的优点,有利于患者术后的快速康复,有助于减少分流管腹腔端的堵塞、腹部并发症和感染的发生。     

同期与分期行脑室-腹腔分流术与颅骨成形术治疗颅脑损伤术后脑积水的疗效分析

目的 对比分析同期和分期行脑室-腹腔分流术（VPS）与颅骨成形术治疗颅脑损伤术后脑积水的效果。方法 回顾性分析2015年9月至2018年4月收治的79例颅脑损伤术后脑积水的临床资料。同期行VPS和颅骨成形术47例（同期组），分期行VPS和颅骨成形术32例（VPS后间隔至少3个月进行颅骨成形术；分期组）。术前、术后7 d采用功能独立性评价量表（FIM）、神经行为认知状况测试（NCSE）评价认知功能情况。术后3个月采用GCS评分、GOS评分评定病人意识及预后情况。结果 术后7 d，两组FIM评分、NCSE评分均明显升高（P<0.05），同期组明显高于分期组（P<0.05）。术后半年内，同期组术后并发症发生率（12.77%，6/47）明显低于分期组（31.25%，10/32；P<0.05）。术后3个月，同期组GCS评分[（12.02±2.87）分]明显高于分期组[（10.09±1.81）分；P<0.05），但是GOS评分[（4.24±0.75）分]与分期组[（3.97±0.70）分]无统计学差异（P>0.05）。结论 对于颅脑损伤术后脑积水，同期和分期行VPS与颅骨成形术，均可有效改善病人认知功能和预后，而同期手术更具优势。     

锁定加压接骨板置入结合自体骨鱼鳞化移植在肱骨干骨折术后骨不愈合中的疗效分析

目的：回顾性评价采用锁定加压接骨板置入结合鱼鳞化自体骨移植治疗肱骨干骨折术后骨不愈合的疗效。 方法：选择2005-08/2009-01郴州市湘南学院附属医院骨科收治的肱骨干骨折术后骨不愈合患者19例,男12例,女7例;年龄28~59岁,平均36岁;全部患者均采用锁定加压接骨板结合自体骨鱼鳞化移植进行治疗,操作要点：上臂后正中入路或外侧入路,首先保护好桡、尺神经,清除骨不愈合部位的瘢痕组织,打通骨髓腔,骨膜做有限剥离。利用微创接骨板内固定技术,接骨板应足够长,骨不愈合的两端至少各有三四枚自锁螺钉固定,锁钉应穿过双侧骨皮质,自体松质骨鱼鳞化植骨。 结果：所有骨不愈合患者全部愈合,愈合时间6~8个月,平均7.2个月。2例术后出现桡神经牵拉性麻痹,经对症处理分别于术后3,6周逐渐恢复。7例仍遗留不同程度肩肘关节功能障碍,但不影响日常生活。无感染、螺钉松动及接骨板折断等并发症发生。 结论：锁定加压接骨板治疗肱骨干骨折术后骨不愈合的优点在于螺钉与接骨板锁定为一体,不会出现单钉折断或接骨板松动的情况,自体松质骨移植与鱼鳞化去皮质技术联用,骨折治愈率更高。     

A long term follow-up of fetal dopaminergic neurons transplantation into the brain of three parkinsonian patients

In three parkinsonian patients ages 48, 53, and 50, human fetal dopaminergic cells taken from the ventral part of mesencephalon of 11-12-week-old fetuses were implanted into the head of caudate nucleus. The operation was carried out with a specially designed device to enable safe and precise graft implantation. All patients had been suffering from severe Parkinson's disease for about 10-15 years (stage 4/5 according to Hoehn and Yahr scale) with bradykinesia, rigidity and tremor as the main symptoms. Long-lasting L-dopa therapy resulted in side effects with ON/OFF syndrome and dyskinesias. A detailed clinical examination was performed before and every 3 months after the operation according to the CAPIT battery of standarized tests. The patients were under post-operational observation lasting 30, 20 and 12 months, respectively. Improvement was observed in all patients starting between 3 and 6 months after operation and is still sustained. Significant increases in movement speed for repeated pronation-supination, finger dexterity and foot lifting tests were found. The speed of walking also increased with decreased rigidity. The OFF phase during the day is of shorter duration and less severe; dyskinesias are markedly reduced. Our results indicate that fetal grafting seems to be a valuable experimental approach towards the treatment of selected parkinsonian patients.