Morphology of the human vertebral endplate

It is presumed that poor intervertebral disc cell nutrition is a contributing factor in degeneration, and is exacerbated by vertebral endplate sclerosis. Yet, quantitative relationships between endplate morphology and degeneration are unavailable. We investigated how endplate bone microstructure relates to indices of disc degeneration, such as morphologic grade, proteoglycan content, and cell density. Intervertebral core samples [n = 96, 14 subjects, L1–L5 level, ages 35–85 (64 ± 16 years), degeneration grade 1 (n = 4), grade 2 (n = 32), grade 3 (n = 44), grade 4 (n = 10), grade 5 (n = 6)] that included subchondral bone, cartilage endplate, and adjacent nucleus were harvested from human cadaveric lumbar spines. The morphology of the vertebral endplate was analyzed using µCT and the adjacent nucleus tissue was collected for biochemical and cellular analyses. Relationships between vertebral endplate morphology and adjacent disc degeneration were analyzed. Contrary to the prevailing notion, vertebral endplate porosity increased between 50% and 130% and trabecular thickness decreased by between 20% and 50% with advancing disc degeneration (p < 0.05). We also observed that nucleus cell density increased (R² = 0.33, p < 0.05) and proteoglycan content decreased (R² = 0.47, p < 0.05) as the endplate became more porous. Our data suggest that endplate sclerosis is not a fundamental factor contributing to disc degeneration. Rather, the opposite was observed in our samples, as the endplate became progressively more porous with age and degeneration. Since ischemic disc cell behavior is commonly associated with degenerative change, this may be related to other factors such as the quality of vertebral capillaries, as opposed to decreased permeability of intervening tissues. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:280–287, 2012     

Endplate deflection is a defining feature of vertebral fracture and is associated with properties of the underlying trabecular bone

Endplate deflection frequently occurs with vertebral failure, but the relationship between the two remains poorly defined. This study examined associations between endplate deflection under compressive loading and characteristics of the neighboring subchondral bone and intervertebral disc (IVD). Ten L1 vertebrae with adjacent IVDs were dissected, compressed axially in a stepwise manner to failure, and imaged with micro‐computed tomography before each loading step. From the images, deflection was measured across the surface of each endplate at each step. Trabecular microstructure and endplate volume fraction were evaluated in 5 mm regions just under the superior endplate. IVDs were assessed using computed tomography and histology. A marked increase in superior endplate deflection coincided with a drop in the load‐displacement curve. Endplate deflection was higher in regions with less robust bone microstructure (p < 0.009), though these associations tended to weaken as loading progressed. Immediately following the ultimate point, endplate deflection was higher in regions underlying the nucleus pulposus versus annulus fibrosus (p = 0.035), irrespective of disc grade (p = 0.346). These results indicate that a sudden increase in endplate deflection signals that the mechanical competence of the vertebra has been compromised. The mechanisms of endplate failure likely relate to anatomical features of the endplate, neighboring trabecular bone, and IVD. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:880–886, 2014.     

Microstructural analysis of three‐dimensional canal network in the rabbit lumbar vertebral endplate

Insufficient nutrient supply through vertebral canal structures to the intervertebral disc (IVD) has been considered as an important contributor for disc degeneration. Despite previous canal structure characterization studies using histology, scanning electron microscopy, and angiography, among others, their three‐dimensional (3D) topology inside the vertebral endplate remains poorly understood. This study aims to characterize the 3D canal structure in the rabbit lumbar vertebral endplate using micro computed tomography (μCT). Vertebral endplates were imaged using high‐resolution μCT with 1.4 × 1.4 × 1.8 μm voxel size. Diameter, length, orientation, and depth starting from the vertebral endplate surface were analyzed for each canal using individual 3D canal models from the vertebral endplate scans. In the layer underneath the vertebral endplate, at a mean depth of 76.2 μm, longitudinally‐oriented relatively short‐length (57.6 μm) and small diameter (45.7 μm) canals were dominant. Large‐scale canals with a mean diameter of 152.1 μm running parallel to the endplate surface were isolated at the depth of 224.1 μm. These canals were connected to both IVD and bone marrow spaces through vertically oriented canals. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:270–276, 2015.     

Micro‐computed tomography evaluation of vertebral end‐plate trabecular bone changes in a porcine asymmetric vertebral tether

We conducted a micro‐CT analysis of subchondral bone of the vertebral end‐plates after application of compressive stress. Thoracic and lumbar vertebral units were instrumented by carrying out left asymmetric tether in eleven 4‐week‐old pigs. After 3 months of growth, instrumented units and control units were harvested. Micro‐CT study of subchondral bone was performed on one central and two lateral specimens (fixated side and non‐fixated side). In control units, bone volume fraction (BV/TV), number of trabeculae (Tb.N), trabecular thickness (Tb.Th), and degree of anisotropy (DA) were significantly higher, whereas intertrabecular space (Tb.Sp) was significantly lower in center than in periphery. No significant difference between the fixated and non‐fixated sides was found. In instrumented units, BV/TV, Tb.N, Tb.Th, and DA were significantly higher in center than in periphery. BV/TV, Tb.N, and Conn.D were significantly higher in fixated than in non‐fixated side, while Tb.Sp was significantly lower. We noted BV/TV, Tb.N, and Tb.Th significantly lower, and Tb.Sp significantly higher, in the instrumented levels. This study showed, in instrumented units, two opposing processes generating a reorganization of the trabecular network. First, an osteolytic process (decrease in BV/TV, Tb.N, Tb.Th) by stress‐shielding, greater in center and on non‐fixated side. Second, an osteogenic process (higher BV/TV, Tb.N, Conn.D, and lower Tb.Sp) due to the compressive loading induced by growth on the fixated side. This study demonstrates the densification of the trabecular bone tissue of the vertebral end‐plates after compressive loading, and illustrates the potential risks of excessively rigid spinal instrumentation which may induce premature osteopenia. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:232–240, 2010     

A morphological study of lumbar vertebral endplates: radiographic, visual and digital measurements

Purpose

Clinical observations suggest that endplate shape and size are related to complications of disc arthroplasty surgery. Yet, the morphology of the vertebral endplate has not been well defined. This study was conducted to characterize the morphology of lumbar vertebral endplates and to quantify their morphometrics using radiographic, visual and digital measures.

Methods

A total of 591 vertebral endplates from 76 lumbosacral spines of men were studied (mean age 51.3 years). The shape of the vertebral endplates was classified as concave, flat and irregular, and was evaluated from both radiographs and cadaveric samples. Each endplate was further digitized using a laser scanner to quantify diameters, surface area and concavity for the whole endplate and its components (central endplate and epiphyseal rim). The morphological characteristics and morphometrics of the vertebral endplates were depicted.

Results

In both radiographic and visual assessments, more cranial endplates (relative to the disc) were concave and more caudal endplates were flat at all disc levels (p < 0.001). On average, the mean concavity depth was 1.5 mm for the cranial endplate and 0.7 mm for the caudal endplate. From L1/2 down to L5/S1 discs, the vertebral endplate gradually changed into a more oval shape. The central endplate was approximately 70 % of the diameter of the whole endplate and the width of the epiphyseal rim varied from 3 to 7 mm.

Conclusions

There is marked morphological asymmetry between the two adjacent endplates of a lumbar intervertebral disc: the cranial endplate is more concave than the caudal endplate. The size and shape of the vertebral endplate also vary considerably between the upper and lower lumbar regions.     

经后路全椎骨切除术治疗僵硬脊柱畸形及并发症分析

目的 探讨采用单纯经后路全椎骨切除技术治疗僵硬性脊柱后凸畸形的手术技术,分析同手术期并发症的发生和预防.方法 回顾性分析2004年10月-2006年7月,采用单纯后路全椎骨切除技术治疗的12例僵硬的脊柱畸形患者.术中完全切除畸形顶椎椎体和相邻椎间盘结构,通过椎弓根钉棒系统综合运用加压-撑开-开放-闭合矫形力获得矫形;椎间以钛网或打压植骨融合.结果 所有患者均获得满意的矢状面和冠状面躯干平衡.术中发生胸膜穿破6例;2例于术中发生凝血机制异常;术后1例有切口下浅层感染.随访时间12～24月,无内l司定松动或断裂发生,遗留后凸及侧凸角度与术后相比平均变化小于5°.结论 僵硬性脊柱畸形矫形手术中最重要的是避免脊髓和腰段神经根损伤.经后路全椎骨切除术能完整显露矫形区域的硬膜囊以直视下保护,且脊髓对一定范围的缩短、成角、旋转等各种位移有耐受性;控制性降压和自体红细胞回输技术能有效减少出血量和输入异体库存血量;术后需关注胸腔并发症.     

骨质疏松性与肿瘤转移性椎体骨折患者代谢指标的比较

目的比较分析骨质疏松性与肿瘤转移性椎体骨折患者相关代谢指标及其关系。方法回顾从2003年01月至2011年06月期间在我院介入血管外科行椎体成形术的146例骨质疏松性椎体骨折患者与111例肿瘤转移性椎体骨折患者的相关代谢指标,运用统计学方法进行统计。统计内容为:性别、年龄、椎体骨折数、手术次数、超敏C-反应蛋白、纤维蛋白原含量、血清总钙、磷、碱性磷酸酶(ALP)、空腹血糖、甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白。结果两组患者在性别、年龄、手术次数、血清碱性磷酸酶、甘油三酯、总胆固醇、高密度脂蛋白水平间有统计学差异(P<0.05)。结论骨质疏松性与肿瘤转移性椎体骨折患者在骨代谢及脂代谢方面存在差异,可帮助临床医生及时找出骨折病因,制定合理的治疗方案。     

X线片上胸腰椎椎板外侧缘及上缘与椎弓根关系研究及应用

[目的]研究胸腰椎椎板外侧缘和上缘与椎弓根的解剖关系，寻找一种新的椎弓根置钉的定位方法。[方法]测量107个正常成人胸腰椎平片的椎板外缘垂线与上缘水平线的交点至椎弓根中心的水平及垂直距离。[结果]获得了相关解剖学数据，发现两者有恒定的关系并成功的临床应用40例。[结论]该研究揭示了椎板外侧缘和上缘与椎弓根的解剖关系，为经椎弓根手术提供了一种新的可靠的解剖学定位方法。     

Incorporation of CT‐based measurements of trunk anatomy into subject‐specific musculoskeletal models of the spine influences vertebral loading predictions

We created subject‐specific musculoskeletal models of the thoracolumbar spine by incorporating spine curvature and muscle morphology measurements from computed tomography (CT) scans to determine the degree to which vertebral compressive and shear loading estimates are sensitive to variations in trunk anatomy. We measured spine curvature and trunk muscle morphology using spine CT scans of 125 men, and then created four different thoracolumbar spine models for each person: (i) height and weight adjusted (Ht/Wt models); (ii) height, weight, and spine curvature adjusted (+C models); (iii) height, weight, and muscle morphology adjusted (+M models); and (iv) height, weight, spine curvature, and muscle morphology adjusted (+CM models). We determined vertebral compressive and shear loading at three regions of the spine (T8, T12, and L3) for four different activities. Vertebral compressive loads predicted by the subject‐specific CT‐based musculoskeletal models were between 54% lower to 45% higher from those estimated using musculoskeletal models adjusted only for subject height and weight. The impact of subject‐specific information on vertebral loading estimates varied with the activity and spinal region. Vertebral loading estimates were more sensitive to incorporation of subject‐specific spinal curvature than subject‐specific muscle morphology. Our results indicate that individual variations in spine curvature and trunk muscle morphology can have a major impact on estimated vertebral compressive and shear loads, and thus should be accounted for when estimating subject‐specific vertebral loading. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2164–2173, 2017.

     

The benefits of photodynamic therapy on vertebral bone are maintained and enhanced by combination treatment with bisphosphonates and radiation therapy

Photodynamic therapy (PDT) has been shown to ablate tumors within vertebral bone and yield short‐term improvements in vertebral architecture and biomechanical strength, in particular when combined with bisphosphonate (BP) treatment. Longer‐term outcomes of PDT combined with current treatments for skeletal metastases are essential to understand its therapeutic potential. The objective of this study is to evaluate the response of vertebrae to PDT after a longer (6‐week) time period, alone and combined with previous BP or radiation treatment (RT). Sixty‐three female rnu/rnu rats were randomized to six treatment groups: untreated control, BP‐only, RT‐only, PDT‐only, combined BP + PDT and combined RT + PDT. L2 vertebrae were structurally analyzed through µCT‐based analysis, axial compressive load‐to‐failure testing and histological analysis of morphology, osteoid formation and osteoclast activity. Combined BP + PDT treatment yielded the largest improvements in bone architecture with combined RT + PDT treatment yielding similar findings, but of a lesser magnitude. Mechanically, ultimate force and stress were correlated to stereological parameters that demonstrated a positive structural effect from combinatory treatment. Increased osteoid formation was observed in both combination therapies without any significant differences in osteoclast activity. Overall, multimodality treatment demonstrated a sustained positive effect on vertebral structural integrity, motivating PDT as a minimally‐invasive adjuvant treatment for spinal metastases. © 2012 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1398–1405, 2013     

老年骨质疏松性椎体压缩骨折和中青年胸腰椎骨折患者椎弓根宽度的CT观察

目的 :观察胸腰椎(T11-L5)骨质疏松性椎体骨折(osteoporotic vertebral fracture,OVF)和中青年椎体骨折患者椎弓根宽度及变化特点。方法:将2012年6月~2015年1月我院收治OVF患者152例作A组,年龄60~95岁平均72.5±7.0岁,BMD-2.5~-5.4SD,平均-3.5±0.65SD;同期收治创伤性胸腰椎骨折患者192例作为B组,年龄26~50岁,平均33.5±4.6岁,BMD未测。均采用CT薄层扫描多平面重建(MPR)技术测量T11~L5各对应脊椎椎弓根宽度(pedicle outer width,POW)。观察两组患者各对应脊椎POW及两组男女性别间各对应脊椎POW差异。两组各对应脊椎POW5mm及7mm的百分比。结果 :两组男性T11~L3各对应脊椎POW大于女性(P0.01)。A组男性T11~L3各对应脊椎POW均小于B组男性(P0.01),A组女性T11~L3各对应脊椎POW均小于B组女性(P0.01)。无论组别及性别L4、L5脊椎POW无显著性差异(P0.05)。POW5mm的百分比:A组占该组椎弓根测量数的11%,分布于T11~L3,其中男性占椎弓根测量数5%,女性占椎弓根测量数13%;B组占椎弓根测量总数的7%,分布于T12~L2,其中男性占椎弓根测量数5%,B组女性占椎弓根测量数11%。POW7mm百分比:A组占所测椎弓根总数的53%,分布于T11~L4,其中男性占椎弓根测量数39%,女性占57%;B组占椎弓根测量数的14%,分布于T11~L3,其中男性占该组椎弓根测量数12%,女性占该组椎弓根测量数19%。结论:在胸腰椎尤其是T11-L3部位,老年OVF组椎弓根宽度明显小于中青年组,女性的椎弓根宽度比男性更小。     

颈椎椎弓根钉内固定研制及置钉准确性研究

目的:设计一种具有纵向撑开和压缩功能的颈椎椎弓根钉内固定,并行颈椎椎弓根钉置钉训练,研究其进钉准确性。方法:(1)收集颈椎新鲜标本7具,先采用CT扫描椎弓根,测量椎弓根内外径的高度和宽度;(2)设计合适的椎弓根钉内固定系统;(3)在收集的7具颈椎新鲜标本70个椎弓根上行置钉操作训练,评价其置钉准确性。结果:颈椎椎弓根直径一般>4.5mm,其高度大于宽度,可适于椎弓根钉内固定使用,颈椎椎弓根钉置钉的准确性高。但颈椎椎弓根存在个体差异,宜行个体化进钉。结论:颈椎椎弓根解剖学上可以满足椎弓根钉内固定的使用。     

Operative treatment of thoraco-lumbar metastases,using methylmetacrylate and Kempf's rods for vertebral replacement and stabilization

Summary The authors report their experience in the treatment of 15 cases in thoracolumbar metastases with spinal cord compression. A decompressive laminectomy was routinely performed and followed by a transversoarthropediculectomy. Most part of the neoplastic tissue was removed from the epidural space, vertebral body and retroperitoneal or retro-pleural areas. Complete decompression of the nervous elements was always achieved. Stabilization was obtained by replacement of the neoplastic vertebral body with a methylmetacrylate prothesis and eventually by Kempf s compression instrumentation. The surgical treatment was completed in a single stage operation, by a classical posterolateral approach. Orthopaedic, neurologic and oncologic advantages of this treatment are discussed.     

骨质疏松性椎体骨折患者胸腰椎椎体后壁形态学测量及临床意义

目的 :探讨骨质疏松性椎体骨折(osteoporotic vertebral fracture,OVF)患者胸椎、腰椎椎体后壁形态学差异及其临床意义。方法:选取我院2013年1月~2016年12月收治的临床资料完整的98例OVF患者,采用CT三维重建技术及多平面重建技术(multiplanar reconstruction,MPR)观察测量T6~L5椎体相关参数。测量椎体纳入标准:椎体无新鲜或陈旧性骨折、无感染征象、无肿瘤性骨质破坏、无半椎体及阻滞椎等先天畸形等;排除标准:已行经皮穿刺椎体后凸成形术(percutaneous kyphoplasty,PKP)治疗的椎体。测量T6~L5椎体CT影像的如下参数:双侧椎体后缘线与椎弓根中轴层面的内侧骨皮质处的交点A、B的连线(AB),骨性椎管凸入椎体顶点O到线AB的距离(OC),椎体最前缘点P到AB的距离(PC),计算R=OC/PC(术中侧位像上骨性椎管凸入椎体深度与椎体中矢状径比值)。采用独立样本t检验比较T12与L1椎体OC值。结果:OC值自T6至T12在3.83±0.13mm到5.21±0.06mm之间,PC值自T6到L5在23.42±0.21mm到44.38±4.51mm之间,均呈逐渐增大趋势。OC值自T12至L5在5.21±0.06mm到0mm之间,呈逐渐减小趋势。R值在T6~T12均接近0.16(1/6),腰椎较胸椎明显减小,在L1~L3明显小于1/6,在L4、L5接近于0。T12与L1的OC值差异有统计学意义(P0.05)。结论 :中下胸椎椎体后壁形态与腰椎相比存在明显差异,OC的存在致中下胸椎椎体后壁在侧位像上的真实投影线位于椎体后1/6处。在中下胸椎行PKP时尽量避免骨水泥分布超过椎体后1/6从而减少骨水泥椎管内渗漏的发生。     

Expression of growth differentiation factor 6 in the human developing fetal spine retreats from vertebral ossifying regions and is restricted to cartilaginous tissues

During embryogenesis vertebral segmentation is initiated by sclerotomal cell migration and condensation around the notochord, forming anlagen of vertebral bodies and intervertebral discs. The factors that govern the segmentation are not clear. Previous research demonstrated that mutations in growth differentiation factor 6 resulted in congenital vertebral fusion, suggesting this factor plays a role in development of vertebral column. In this study, we detected expression and localization of growth differentiation factor 6 in human fetal spinal column, especially in the period of early ossification of vertebrae and the developing intervertebral discs. The extracellular matrix proteins were also examined. Results showed that high levels of growth differentiation factor 6 were expressed in the nucleus pulposus of intervertebral discs and the hypertrophic chondrocytes adjacent to the ossification centre in vertebral bodies, where strong expression of proteoglycan and collagens was also detected. As fetal age increased, the expression of growth differentiation factor 6 was decreased correspondingly with the progress of ossification in vertebral bodies and restricted to cartilaginous regions. This expression pattern and the genetic link to vertebral fusion suggest that growth differentiation factor 6 may play an important role in suppression of ossification to ensure proper vertebral segmentation during spinal development. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:279–289, 2016.     

早期后路椎管减压伤椎椎弓根螺钉内固定治疗中上胸椎骨折脱位

目的探讨早期后路椎管减压伤椎椎弓根螺钉内固定治疗中上胸椎骨折脱位伴脊髓损伤的临床效果。方法对41例中上胸椎骨折脱位患者49椎采用早期后路椎管减压伤椎椎弓根螺钉内固定植骨融合,固定节段4～6节。患者均在72 h内手术。结果 41例均获随访,时间12～46(28±2)个月。脊髓神经功能按ASIA分级:A级6例恢复至B级4例,2例无恢复;B级10例恢复至C级6例、D级3例、1例无恢复;C级15例恢复至D级9例、E级2例,4例无恢复;D级6例恢复至E级3例,3例无恢复;E级4例仍为E级。椎体前缘高度:术前为35.36%±7.48%,术后纠正到91.48%±2.15%,末次随访时为90.56%±1.63%;Cobb角:术前为37°±8°,术后及末次随访为-4°±2°。骨折脱位完全复位,无内固定松动及断裂,末次随访均达到骨性融合。结论早期后路椎管减压伤椎椎弓根螺钉内固定是治疗急性中上胸椎骨折脱位的有效方法,能达到椎体早期复位和脊髓减压目的 ,利于患者早期康复。     

颈椎小关节脱位与闭合性椎动脉损伤的相关性研究

[目的]探讨颈椎小关节脱位与闭合性椎动脉损伤的相关性。[方法]本组319仍颈椎创伤患者，颈椎骨折261例；小关节脱位46例，其中单侧小关节脱位22例，双侧小关节脱位24例；无放射影像异常的脊髓损伤12例。所有患者接受了颈椎MRI和椎动脉2DTOF MRA的前瞻性检查。动物实验建立犬颈椎小关节脱位的撞击模型，撞击后摄颈椎X线片，24—36h后行椎动脉2DTOF MRA检查。[结果]临床319例颈椎创伤患者，52例继发有椎动脉损伤，单侧51例，双侧1例。发现有椎动脉损伤的患者中，34例（65．4％）原始损伤为颈椎小关节脱位，16例为颈椎骨折，2例为无放射影像异常的颈髓损伤。动物实验14只犬撞击后发生颈椎小关节脱位，12只犬无小关节脱位。14只发生小关节脱位犬中，8只继发有单侧椎动脉损伤，12只无小关节脱位犬均无椎动脉损伤。[结论]闭合性椎动脉损伤最常继发于颈椎小关节脱位，瞬间位移使椎动脉受到过度牵张是主要的致伤因素。     

体表脊柱侧位节段定位板的研制及临床应用

目的: 研制体表脊柱侧位节段定位板,探讨其在胸腰椎节段定位的临床应用效果。方法: 自2018 年3 月 至2021年3 月老年患者因胸腰椎压缩性骨折行经皮椎体球囊扩张后凸成形手术共768 例,男356例,女412例;年龄64~92(77.9±13.5)岁。均伤后1 周内来院治疗。所有患者进行术前定位,按照定位方法不同分为定位板组和定位器组。定位板组390 例,男180例,女210例,年龄64~92(78.4±14.3)岁。定位器组378例,男176例,女202例,年龄64~90(77.5±13.4)岁。用上述两种方法初步定位后做好皮肤标记,常规消毒铺巾,在标记点及近尾端垂直身体刺入细针头后透视脊柱侧位,评价原定位方法的准确率,对两组定位透视次数、定位时间和定位准确性。结果: 定位板组和定位器组透视次数分别为(3.3±0.5) 次和(5.0±1.2)次,定位时间分别为(60.4±9.4) s和(105.0±30.9) s,透视准确率分别为97.5 %(380/390)和85.6 %(324/378),差异有统计学意义(P<0.05)。结论: 体表脊柱侧位节段定位板具有操作简便、定位准确,患者接受X 线辐射次数少的优点。     

Development of the blood-testis barrier and changes in vascular permeability at puberty in rats

The effectiveness of the blood-testis barrier to water-soluble substances was assessed in rats of various ages by measuring the volumes of distribution of Cr-EDTA and albumin, and estimating the proportion of the testis made up by interstitial tissue and tubular lumen by morphometric techniques on cryostat sections of frozen tissue. The interstitial tissue volume fell from 15 days to reach adult values at about 30 days of age. A lumen was present in some animals at 15 days, and it enlarged progressively to reach adult levels at about 45 days of age. The 1-h Cr-EDTA space began to fall after 25 days, and reached adult values by 33 days; in rats aged 25 and 30 days, the Cr-EDTA space was almost twice the measured interstitial tissue volume, but even in the older rats, the Cr-EDTA space remained appreciably greater than the interstitial tissue volume. The 20-h albumin space did not begin to fall until after 33 days, and had still not reached adult values in rats aged 44 days. Thus, the functional barrier to water-soluble markers develops later and more gradually than the barrier to electron-opaque markers as used by previous authors, and its appearance correlates more closely with enlargement of the tubular lumen than with formation of the inter-Sertoli cell junctions. The rate at which the albumin space approached its final value was used to calculate the vascular permeability to albumin. This rose to a maximum between 25 days and 33 days of age, and then fell again, although adult values had still not been reached by 44 days of age.