Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

With chromium-hematoxylin staining, we found evidence for the existence of novel age-dependent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-weekold rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-dependent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increasing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix.

Dura Mater: Anatomy and Clinical Implication

The dura mater is of similar embryological origin to the fascial organ. It contains several fibroblasts which make the dura mater a flexible structure. Dura mater is the outermost of the three layers of meninges, a thick and rigid inelastic membrane that covers the brain and spinal cord and that is impermeable to the cerebrospinal fluid. The cranial dura mater in certain respects differs anatomically from the dura material in the spinal cord, and it is important to classify them separately. This article reviews the anatomical structure of spinal and cranial dura mater and its anatomy with muscle, fascia, bone structure and ligaments. Dura mater is a structure in the body that is connected with systemic functions.

Meningioma originating from the superior petrosal vein without dural attachment:A case report

BACKGROUND Meningioma in the cerebellopontine angle(CPA)without dural attachment is extremely rare.We report a unique case of meningioma derived from the superior petrosal vein without dural attachment.CASE SUMMARY A 44-year-old right-handed woman presented with a two-month history of headache and tinnitus.Brain magnetic resonance imaging showed a well-defined contrast-enhancing lesion in the right CPA without a dural tail sign.Tumor resection was performed using a right retro sigmoid approach.A dural attachment was not seen at the tentorium or posterior surface of the petrous pyramid.The tumor was firmly adherent to the superior petrosal vein.The origin site was cauterized and resected with the preservation of the superior petrosal vein.A diagnosis of meningothelial meningioma was made.The patient’s headache and tinnitus gradually disappeared,and a recurrence was not observed five years after the surgery.CONCLUSION The rare occurrence of meningioma without dural attachment makes it difficult to determine dural attachment before surgery.The absence of dural attachment makes it easy to completely resect such tumors.Vessels related to tumors should be removed carefully,considering the possible presence of tumor stem cells in the microvessels.

Preliminary exploration of the development of a collagenous artificial dura mater for sustained antibiotic release

Background Intracranial infection is one of the most common complications of open craniocerebral injury and of conventional craniotomy in neurosurgery. The presence of blood-brain barrier leads to lower drug concentrations in the cerebrospinal fluid than in the venous blood. Increasing the intravenous dosage or frequency carries the risk of systemic adverse reactions or infections in other parts of the body. Developing an artificial dura mater （ADM） for sustained antibiotic release for use during neurosurgery can solve the problems perfectly. Methods Three types of drug-loaded ADMs made of collagen and containing cefuroxime sodium, ceftriaxone sodium, or norvancomycin were prepared. The antibacterial activity and sustained release characteristics of the ADMs were examined using bacteriostatic and release tests. Results Single-layered collagen based ADMs （40 mm×50 mm×5 mm） containing 18 mg cefuroxime sodium or ceftriaxone sodium were not suitable for continued development because of drug preservation and stability issues. Using smaller ADMs （20 mm30 mm×7 mm）, containing 4.86 mg of norvancomycin, with increased collagen density and a three-layered film with two outer drug-free films above and below the antibiotic layer resulted in sustained cumulative release of 2.91 mg （59.9%） of norvancomycin over 72 hours. The similar factor （f2） comparison method proved that products from a same batch were statistically significant similar （f2 〉50）. Conclusions Artificial ADMs made of collagen can be processed to provide a mature dural repair material for the sustained release of norvancomycin. This system may provide a basis for developing sustained release materials for other drugs.

Electrohydrodynamic Fabrication of Triple-layered Polycaprolactone Dura Mater Substitute with Antibacterial and Enhanced Osteogenic Capability

In the field of dura mater repair,it is essential to employ artificial substitutes mimicking the multilayered microar-chitecture and multiple functions of native dura mater for effective neurosurgery.However,existing artificial dura mater substitutes commonly cause complications because of mismatched structural and mechanical properties as well as the lack of antibacterial activity or osteogenic capability.In this study,a triple-layered dura mater substi-tute was fabricated by electrohydrodynamic(EHD)jetting techniques,including electrospinning and melt-based EHD printing processes.Highly aligned polycaprolactone(PCL)nanofibers loaded with gentamicin sulfate(GS)were prepared by electrospinning to form the inner layer,which can mimic the aligned collagen fibers of the native dura mater.Random PCL-GS nanofibers were then deposited by electrospinning to form the middle layer.They were intended to enhance the mechanical properties of the fabricated scaffolds.The outer layer involv-ing PCL microfibers doped with nano-hydroxyapatite(nHA)at various angles was printed by the melting-based EHD method,which can enhance osteogenic capability and promote the fusion between the dura mater substi-tute and the skull.The tensile strength of the triple-layered drug-loaded biomimetic dura mater substitute was 22.42±0.89 MPa,and the elongation at break was 36.43%±2.00%.The addition of GS endowed the substitutes with an anti-infection property without influencing their cytocompatibility.Furthermore,the incorporation of nHA promoted the osteogenic differentiation of MC3T3-E1 cells seeded on the triple-layered scaffolds.This work offers a promising strategy to manufacture multilayered dura mater substitutes with the desired antibacterial and enhanced osteogenic capability performance,possibly providing a novel candidate for dural tissue repair.

耳内镜下鼓膜修补术后穿孔再修补的疗效分析

目的 探讨人工硬脑膜和表皮生长因子在耳内镜下鼓膜修补术后鼓膜穿孔再修补中的临床疗效。方法 选择该院耳内镜下鼓膜修补术后复查时仍有鼓膜穿孔未愈合的患者58例,随机分为A组和B组,各29例。A组采用明胶海绵修补鼓膜穿孔,B组采用人工硬脑膜和表皮生长因子修补鼓膜穿孔,每个月复查鼓膜愈合情况,3个月后复查纯间测听。结果 A组修补成功率为34.48%(10/29),B组修补成功率为75.86%(22/29),两组患者比较,差异有统计学意义(P <0.05);A组气骨导差改善(7.32±2.68) dB HL,B组气骨导差改善(21.77±4.65)dB HL,两组患者比较,差异有统计学意义(P <0.05)。结论 人工硬脑膜是合适的鼓膜再生支架,表皮生长因子可促进鼓膜穿孔愈合,两者结合使用是鼓膜再修补的一种可行的治疗方案。

大鼠硬脑膜对颅骨成骨增强的影响

背景:硬脑膜与颅骨在结构和功能上联系密切,原代提取硬脑膜和颅骨细胞并将二者共培养的研究几乎没有,利用原代细胞探究硬脑膜对颅骨的影响具有创新性,有望为临床治疗提供理论依据。目的:原代提取大鼠硬脑膜和颅骨细胞,观察硬脑膜对颅骨增殖和分化能力的影响,初步了解Twist1在其中的作用。方法:利用酶解法与组织块法相结合的方法原代提取出生3 d内大鼠硬脑膜细胞和颅骨细胞,免疫荧光染色鉴定所提取细胞,茜素红染色鉴定与评估颅骨细胞及其矿化能力,real-time PCR检测硬脑膜细胞与颅骨细胞共培养后,颅骨细胞增殖与成骨相关基因表达及Twist1的表达。结果与结论:①形态学:所提取硬脑膜细胞形态特征与成纤维细胞一致,成骨细胞呈纺锤形。②细胞鉴定:免疫荧光染色显示,所提取硬脑膜细胞表达高水平的波形蛋白,颅骨细胞表达高水平的碱性磷酸酶;成骨诱导28 d颅骨细胞茜素红染色观察到明显的矿化结节。③real-time PCR检测显示,与对照组比较,共培养组PCNA、碱性磷酸酶、RUNX2 mRNA表达升高(P<0.01);Twist1 mRNA表达降低(P<0.01)。④结果表明,原代提取的颅骨细胞具有较强的矿化能力,硬脑膜是促进颅骨的生长发育与成骨分化的重要因素,且Twist1在该过程中发挥重要作用。

颅缝发育与颅缝早闭的分子机制

颅骨的发育依赖于颅缝(cranial suture)正常的骨供给,期间颅缝的间充质干细胞经历系统地增殖和成骨分化以保证骨的正常生长。遗传因素或外界干扰则可能引起干细胞的过度成骨分化,导致颅骨的过早闭合,称为颅缝早闭。颅缝细胞与细胞外基质、骨膜以及脑膜共同构成颅缝微环境(niche)。它们相互调节以保证颅缝的正常发育。临床研究发现,绝大多数颅缝早闭(craniosynostosis)患者都伴有硬脑膜和细胞外基质(extracellular matrixc,ECM)的异常。许多研究也发现,作用于颅缝的异常外界机械刺激也可能导致颅缝发育的异常。考虑到颅缝发育受多方面因素影响,本篇综述将介绍近年来有关颅缝微环境异常,以及机械力在调控颅缝发育中的研究进展,总结颅缝早闭发生的分子机制和目前研究方向,旨在为该病的诊断治疗提供新的思路。

Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease

Impaired amyloid-β clearance from the brain is a core pathological event in Alzheimer＇s disease.The therapeutic effect of current pharmacotherapies is unsatisfactory,and some treatments cause severe side effects.The meningeal lymphatic vessels might be a new route for amyloid-β clearance.This study investigated whether promoting dural lymphangiogenesis facilitated the clearance of amyloid-β from the brain.First,human lymphatic endothelial cells were treated with 100 ng/m L recombinant human vascular endothelial growth factor-C（rh VEGF-C） protein.Light microscopy verified that rh VEGF-C,a specific ligand for vascular endothelial growth factor receptor-3（VEGFR-3）,significantly promoted tube formation of human lymphatic endothelial cells in vitro.In an in vivo study,200 μg/m L rh VEGF-C was injected into the cisterna magna of APP/PS1 transgenic mice,once every 2 days,four times in total.Immunofluorescence staining demonstrated high levels of dural lymphangiogenesis in Alzheimer＇s disease mice.One week after rh VEGF-C administration,enzyme-linked immunosorbent assay results showed that levels of soluble amyloid-β were decreased in cerebrospinal fluid and brain.The Morris water maze test demonstrated that spatial cognition was restored.These results indicate that the upregulation of dural lymphangiogenesis facilities amyloid-β clearance from the brain of APP/PS1 mice,suggesting the potential of the VEGF-C/VEGFR-3 signaling pathway as a therapeutic target for Alzheimer＇s disease.

人工硬脑膜DuraGen^(TM)植入转归的实验研究

目的通过动物实验,观察人工生物型硬脑膜DuraGenTM植入后的转归过程。方法将DuraGenTM修补于15头实验猪右侧硬膜缺损处,左侧作为对照。在修补后1、3、6个月分别处死5头实验猪,行大体标本、光镜和电镜检查,观察人工生物型硬脑膜修补对硬脑膜缺损的作用。结果新生自体纤维组织逐步建立于植入物内,形成一个由新生纤维组织和植入物支架组织交织在一起的中间态结构。新生纤维组织逐渐增加,植入支架结构逐步吸收并最终被新生纤维组织所替代。结论人工生物型脑膜DuraGenTM具有良好的组织相容性,是目前理想的硬脑膜修补材料。

骨形态发生蛋白2在小儿颅骨缺损自行修复中的作用

颅脑外伤在小儿各类外伤中占据首位。去骨瓣减压术为神经外科常见减少颅内压的手术方式,颅骨缺失会导致患儿脑组织缺少颅骨保护,颅骨作为脑组织最直接的保护屏障,若缺损不及时修补会因体位、情绪和腹压等会导致脑组织在颅内发生移动,从而造成脑穿通性畸形、癫痫发作和脑变性萎缩等疾病。小儿有好动、依从性差、自我保护能力差等特点,更容易形成二次伤害。小儿处于生长发育期,缺乏颅骨的保护,颅脑容易受到二次伤害,还会影响患儿神经系统的正常发育,造成患儿智力低下,神经系统发育不完善等相关并发症,所以重建颅骨的完整对患儿的生长发育至关重要。未成熟硬脑膜对颅骨的发育和缺损修复有重要作用,2岁以下的儿童能够修复巨大的颅骨缺损,而成年人则缺乏这种内源性能力。幼龄动物骨缺损中骨形态发生蛋白2(BMP2)上调,表明BMP2在骨组织再生中具有重要作用。许多生物调节因子可调控BMP2的活性。该综述就BMP2在小儿颅骨缺损修复中的研究现状做总结。

硬膜替代材料Dura-L移植后的形态学与免疫原性研究

目的研究新型硬膜替代材料Dura-L移植后的形态学与免疫原性。方法选用40只成年雄性家兔,随机等分成5组:A:单侧自体移植无创组,B:单侧自体移植创伤组,C:单侧Dura-L移植加对侧自体移植无创组,D:单侧Dura-L移植加对侧自体移植创伤组,E:单侧阳性对照膜移植无创组。应用显微外科技术在无菌条件下施行硬膜替代手术,将Dura-L移植于C、D组兔脑表面。分别于2周、1个月、3个月应用扫描电镜、免疫荧光、病理学切片检测进行评价。结果2周末、1个月末、3个月末C组、D组与E组间在表面光滑程度、荧光强度、炎性细胞浸润三方面之间的差异具有统计学意义,而与A、B两组间的差异不具有统计学意义。结论Dura-L移植后形态学与家兔硬膜类似,免疫原性低,是一种比较适合的硬膜替代材料。

Effect of visual stimulus locations on pattern-reversal visual evoked potential An epidural electrocorticogram study

To explore the effect of the location of a visual stimulus on neural responses in the primary visual cortex （V1）, a micro-electromechanical system-based microelectrode array with nine channels was implanted on the cerebral dura mater of V1 in adult cats. 2 Hz pattern reversal checkerboard stimul were used to stimulate the four visual quadrants （i.e., upper left, upper right, lower left, and lower right fields）. The results showed that there was a N75 component of the visual evoked potential around 50-80 ms after the onset of a checkerboard stimulus, and the onset of these N75 peaks varied with different stimulus locations. The checkerboard stimuli Jnduced shorter latencJes in the contralateral V1 than in the ipsilateral V1, while the checkerboard stimulus in the upper half visual field induced shorter latencies for N75. These results suggested that the pattern-reversal stimuli induced neural activities in V1 that can be recorded with multichannel microelectrodes, and more detailed temporal and spatial properties can be measured.

Intradural Disc Herniation Can Be Intra-Arachnoid or Extra-Arachnoid: 2 Case Reports with MRI Diagnosis and Non-Surgical Management

Intradural disc herniation is rare and often diagnosed during surgery. We present two patients with the disease, one with an intra-arachnoid type, the other with an extra-arachnoid location. The teaching point of those cases is that this very frequent pathology can take a variety of forms, depending on the structures that are infiltrated. The key point in correctly diagnosing the intradural disc herniation is to look at the angle between the fragment and the dura. Is it pushing it (as in the usual disc herniation), embedded in it (those with the extra-arachnoid type) or does it go through to fall into the CSF (In the intra-arachnoid type)? It could be diagnosed on MRI preoperatively. Contrary to many published cases of intradural disc herniation, the two patients could be managed non-surgically.

Use of Acellular Fish Skin for Dura Repair in an Ovine Model: A Pilot Study

Recently the use of biologic materials as dura mater repair patches has been increasing. The purpose of this study is to assess the basis for efficacy and safety of using a novel fish derived acellular dermis (Kerecis Omega3 DuraTM). In an ovine model a craniotomy under general anaesthesia was performed. A defect was produced in the dural covering of approximately 1 × 2 cm and closed with an onlay technique, with Kerecis Omega3 Dura. The bone defect was covered with the bony flap and the overlying tissues closed in layers. At 2, 5, 8 and 11 weeks the sheep underwent MRI scanning followed by euthanasia, necropsy and histological assessment. MRI images taken at 2, 5, 8 and 11 weeks showed initially moderate inflammatory response, which diminished over time, and at 11 weeks no evidence of inflammation existed. There was evidence of cerebrospinal fluid leakage at no time point. Necropsy revealed some adhesions at 5 and 8 weeks, in particular at 5 weeks, but at 11 weeks there were no adhesions found. From 2 - 11 weeks, there was evidence of initially an inflammatory reaction followed by neodura formation at the defect site through cellular ingrowth and remodeling of the acellular fish skin. Histology showed a histiocytic foreign body reaction initially that subsided over time. As early as 8 weeks there was evidence of neodura formation and by 11 weeks there was a minimal inflammatory response with an intact neodura formed. In this pilot study the Kerecis Omega3 Dura patches performed in a safe and efficacious manner. This new material needs to be fully assessed and compared with other products that are currently on the market in a larger scale animal study.

小脑幕硬膜型海绵状血管瘤一例

本研究遵守《赫尔辛基宣言》,经湖北省肿瘤医院伦理委员会批准,免除受试者知情同意,批准文号:LLHBCH2022YN-048。患者男,57岁,无明显诱因出现左下肢麻木1月余。体格检查及实验室辅助检查未见异常。MRI检查:幕下小脑后方右侧近中线旁约4.4 cm×2.8 cm的肿物,边缘光整,信号欠均,T1WI呈低信号,内伴条片状高信号(图1A),T2WI呈高信号.

Clinical characteristics and risk factors of intracranial hemorrhage after spinal surgery

BACKGROUND Intracranial hemorrhage after spinal surgery is a rare and devastating complication.AIM To investigate the economic burden,clinical characteristics,risk factors,and mechanisms of intracranial hemorrhage after spinal surgery.METHODS A retrospective cohort study was conducted from January 1,2015,to December 31,2022.Patients aged≥18 years,who had undergone spinal surgery were included.Intracranial hemorrhage patients were selected after spinal surgery during hospitalization.Based on the type of spinal surgery,patients with intracranial hemorrhage were randomly matched in a 1:5 ratio with control patients without intracranial hemorrhage.The patients'pre-,intra-,and post-operative data and clinical manifestations were recorded.RESULTS A total of 24472 patients underwent spinal surgery.Six patients(3 males and 3 females,average age 71.3 years)developed intracranial hemorrhage after posterior spinal fusion procedures,with an incidence of 0.025%(6/24472).The prevailing type of intracranial hemorrhage was cerebellar hemorrhage.Two patients had a poor clinical outcome.Based on the type of surgery,30 control patients were randomly matched in 1:5 ratio.The intracranial hemorrhage group showed significant differences compared with the control group with regard to age(71.33±7.45 years vs 58.39±8.07 years,P=0.001),previous history of cerebrovascular disease(50%vs 6.7%,P=0.024),spinal dura mater injury(50%vs 3.3%,P=0.010),hospital expenses(RMB 242119.1±87610.0 vs RMB 96290.7±32029.9,P=0.009),and discharge activity daily living score(40.00±25.88 vs 75.40±18.29,P=0.019).CONCLUSION The incidence of intracranial hemorrhage after spinal surgery was extremely low,with poor clinical outcomes.Patient age,previous stroke history,and dura mater damage were possible risk factors.It is suggested that spinal dura mater injury should be avoided during surgery in high-risk patients.

基质金属蛋白酶对促进外伤性硬膜下积液转化为慢性硬膜下血肿的作用

目的分析基质金属蛋白酶对促进外伤性硬膜下积液转化为慢性硬膜下血肿的作用。方法选取2021年2月—2022年7月龙岩市第二医院的200例慢性硬膜下血肿患者,患者入院后均常规采集外周血液标本,并选取最终发展为硬膜下血肿的24例患者为研究对象,回顾性分析患者的临床资料,患者均进一步接受明胶酶谱法检测,检测内容主要为积液转化为慢性硬膜下血肿前后外周血的基质金属蛋白酶活性,检测指标主要为:基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)活性,并按照规范方法对血肿内膜中的MMP-2和MMP-9活性和血肿外膜的MMP-2和MMP-9活性进行检测,对比血清液和血肿外膜中的MMP-2、MMP-9活性,另外对血肿液和血清液中的MMP-2、MMP-9活性进行对比。结果血肿液的MMP-2、MMP-9活性均显著高于血清液(P<0.05);血肿外膜的MMP-2、MMP-9活性显著高于血肿内膜(P<0.05)。结论基质金属蛋白酶是促进外伤性硬膜下积液转化为慢性硬膜下血肿的危险因素,其作用部位主要为血肿外膜,因此在外伤性硬膜下积液患者诊治中需积极加强对基质金属蛋白酶的监测,特别是对MMP-2、MMP-9活性的监测,以预防硬膜下积液转化为慢性硬膜下血肿。

IgG4相关性肥厚性硬脑膜炎的诊治进展

IgG4相关性疾病是一类比较少见的、涉及全身系统的疾病,由免疫介导,产生慢性炎症伴纤维化。因受累器官系统不同而临床症状各异,波及中枢神经系统时,硬脑膜常受累而致IgG4相关性肥厚性硬脑膜炎(IgG4-RHP)的发生,其病因和发病机制未明。患者多以头痛就诊,脑脊液及血清检查可见IgG4水平高于正常,还可出现典型影像学特征,硬脑膜不同程度增厚或占位改变。该病于我国首先报道,为进一步加深认识,避免过度诊断或漏诊,本文结合IgG4-RD的研究进展进行阐述。

神经电生理监测下手术治疗腰段脊髓硬膜动静脉瘘1例报告

硬膜动静脉瘘(SDAVF)是位于硬膜背侧表面的神经根动脉与神经根静脉之间形成异常动静脉分流,进而引起静脉高压和扩张,使脊髓灌注减少甚至受压,导致脊髓缺血和水肿[1-4]。SDAVF属于脊髓血管畸形,目前具体病因尚不清楚,可能与先天性血管畸形有关。好发于中年男性[5-6],发生率为5/106~10/106,常累及胸腰段[7],临床表现为感觉、运动功能逐步下降,有时伴有疼痛、括约肌功能失调,症状进行性加重[8-11]。本院2022年2月17日收治1例经数字减影血管造影(DSA)检查确诊的SDAVF患者,手术治疗后患者症状明显缓解,现将诊疗过程进行总结,报告如下。