Effects of surface profile on porcine dural mechanical properties.

BACKGROUND: Cerebrospinal fluid leakage through the spinal meninges is difficult to diagnose and treat. Moreover, its underlying mechanism remains unknown. Considering that the dura mater is structurally the strongest and outermost membrane among the three-layered meninges, we hypothesized that a dural mechanical tear would trigger spontaneous cerebrospinal fluid leakage, especially when a traumatic loading event is involved. Thus, accurate biomechanical properties of the dura mater are indispensable for improving computational models, which aid in predicting blunt impact injuries and creating artificial substitutes for transplantation and surgical training. METHOD: We characterized the surface profile of the spinal dura and its mechanical properties (Young's moduli) with a distinction of its inherent anatomical sites (i.e., the cervical and lumbar regions as well as the dorsal and ventral sides of the spinal cord). FINDINGS: Although the obtained Young's moduli exhibited no considerable difference between the aforementioned anatomical sites, our results suggested that the wrinkles structurally formed along the longitudinal direction would relieve stress concentration on the dural surface under in vivo and supraphysiological conditions, enabling mechanical protection of the dural tissue from a blunt impact force that was externally applied to the spine. INTERPRETATION: This study provides fundamental data that can be used for accurately predicting cerebrospinal fluid leakage due to blunt impact trauma.

The relationship between myodural bridge, atrophy and hyperplasia of the suboccipital musculature, and cerebrospinal fluid dynamics.

The Myodural Bridge (MDB) is a physiological structure that is highly conserved in mammals and many of other tetrapods. It connects the suboccipital muscles to the cervical spinal dura mater (SDM) and transmits the tensile forces generated by the suboccipital muscles to the SDM. Consequently, the MDB has broader physiological potentials than just fixing the SDM. It has been proposed that MDB significantly contributes to the dynamics of cerebrospinal fluid (CSF) movements. Animal models of suboccipital muscle atrophy and hyperplasia were established utilizing local injection of BTX-A and ACE-031. In contrast, animal models with surgical severance of suboccipital muscles, and without any surgical operation were set as two types of negative control groups. CSF secretion and reabsorption rates were then measured for subsequent analysis. Our findings demonstrated a significant increase in CSF secretion rate in rats with the hyperplasia model, while there was a significant decrease in rats with the atrophy and severance groups. We observed an increase in CSF reabsorption rate in both the atrophy and hyperplasia groups, but no significant change was observed in the severance group. Additionally, our immunohistochemistry results revealed no significant change in the protein level of six selected choroid plexus-CSF-related proteins among all these groups. Therefore, it was indicated that alteration of MDB-transmitted tensile force resulted in changes of CSF secretion and reabsorption rates, suggesting the potential role that MDB may play during CSF circulation. This provides a unique research insight into CSF dynamics.

Corneal injury is associated with stromal and vascular alterations within cranial dura mater.

The cornea and cranial dura mater share sensory innervation. This link raises the possibility that pathological impulses mediated by corneal injury may be transmitted to the cranial dura, trigger dural perivascular/connective tissue nociceptor responses, and induce vascular and stromal alterations affecting dura mater blood and lymphatic vessel functionality. In this study, using a mouse model, we demonstrate for the first time that two weeks after the initial insult, alkaline injury to the cornea leads to remote pathological changes within the coronal suture area of the dura mater. Specifically, we detected significant pro-fibrotic changes in the dural stroma, as well as vascular remodeling characterized by alterations in vascular smooth muscle cell (VSMC) morphology, reduced blood vessel VSMC coverage, endothelial cell expression of the fibroblast specific protein 1, and significant increase in the number of podoplanin-positive lymphatic sprouts. Intriguingly, the deficiency of a major extracellular matrix component, small leucine-rich proteoglycan decorin, modifies both the direction and the extent of these changes. As the dura mater is the most important route for the brain metabolic clearance, these results are of clinical relevance and provide a much-needed link explaining the association between ophthalmic conditions and the development of neurodegenerative diseases.

A mesothelium divides the subarachnoid space into functional compartments.

The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that compartmentalizes the subarachnoid space in the mouse and human brain, designated the subarachnoid lymphatic-like membrane (SLYM). SLYM is morpho- and immunophenotypically similar to the mesothelial membrane lining of peripheral organs and body cavities, and it encases blood vessels and harbors immune cells. Functionally, the close apposition of SLYM with the endothelial lining of the meningeal venous sinus permits direct exchange of small solutes between cerebrospinal fluid and venous blood, thus representing the mouse equivalent of the arachnoid granulations. The functional characterization of SLYM provides fundamental insights into brain immune barriers and fluid transport.

The relationship between compensatory hyperplasia of the myodural bridge complex and reduced compliance of the various structures within the cranio-cervical junction.

The myodural bridge complex (MDBC) is described as a functional anatomic structure that involves the dense connective tissue fibers, muscles, and ligaments in the suboccipital region. It has recently been proposed that the MDBC can influence cerebrospinal fluid (CSF) circulation. In the present study, bleomycin (BLM), a type of antibiotic that is poisonous to cells, was injected into the posterior atlanto-occipital interspace (PAOiS) of rats to induce fibrous hyperplasia of structures in PAOiS. Sagittal sections of tissues obtained from the posterior-occipital region of the rats were stained utilizing the Masson Trichrome staining method. Semiquantitative analysis evidenced that the collagen volume fraction of collagen fibers of the MDBC, as well as the sum of the area of the spinal dura mater and the posterior atlanto-occipital membrane in the BLM group were significantly increased (p < .05) compared to that of the other groups. This finding illustrates that the MDBC fibers as well as other tissues in the PAOiS of rats in the BLM group developed fibrotic changes which reduced compliance of the spinal dura mater. Indeed, the sectional area of the rectus capitis dorsal minor muscle in the BLM group was measured to be increased. These changes may further restrict CSF flow. The present research provides support for the recent hypothesis proposed by Labuda et al. concerning the pathophysiology observed in symptomatic adult Chiari malformation Type I patients, that there exists a relationship between the altered compliance of the anatomic structures within the craniocervical region and the resultant compensatory hyperplasia of the MDBC.

Dynamic load response of human dura mater at different velocities.

Despite of its assumed role to mitigate brain tissue response under dynamic loading conditions, the human dura mater is frequently neglected in computational and physical human head models. A reason for this is the lack of load-deformation data when the dura mater is loaded dynamically. To date, the biomechanical characterization of the human dura mater predominantly involved quasi-static testing setups. This study aimed to investigate the strain rate-dependent mechanical properties of the human dura mater comparing three different velocities of 0.3, 0.5 and 0.7 m/s. Samples were chosen in a perpendicular orientation to the visible main fiber direction on the samples' surface, which was mostly neglected in previous studies. The elastic modulus of dura mater significantly increased at higher velocities (5.16 [3.38; 7.27] MPa at 0.3 m/s versus 44.38 [35.30; 74.94] MPa at 0.7 m/s). Both the stretch at yield point λf (1.148 [1.137; 1.188] for 0.3 m/s, 1.062 [1.054; 1.066] for 0.5 m/s and 1.015 [1.012; 1.021] for 0.7 m/s) and stress at yield point σf of dura mater (519.14 [366.74; 707.99] kPa for 0.3 m/s versus 300.52 [245.31; 354.89] kPa at 0.7 m/s) significantly decreased with increasing velocities. Conclusively, increasing the load application velocity increases stiffness and decreases tensile strength as well as straining potential of human dura mater between 0.3 and 0.7 m/s. The elastic modulus of human dura mater should be adapted to the respective velocities in computational head impact simulations.

The relationship between myodural bridges, hyperplasia of the suboccipital musculature, and intracranial pressure.

During mammalian evolution, the Myodural Bridges (MDB) have been shown to be highly conserved anatomical structures. However, the putative physiological function of these structures remains unclear. The MDB functionally connects the suboccipital musculature to the cervical spinal dura mater, while passing through the posterior atlanto-occipital and atlanto-axial interspaces. MDB transmits the tensile forces generated by the suboccipital muscles to the cervical dura mater. Moreover, head movements have been shown to be an important contributor to human CSF circulation. In the present study, a 16-week administration of a Myostatin-specific inhibitor, ACE-031, was injected into the suboccipital musculature of rats to establish an experimental animal model of hyperplasia of the suboccipital musculature. Using an optic fiber pressure measurement instrument, the present authors observed a significant increase in intracranial pressure (ICP) while utilizing the hyperplasia model. In contrast, surgically severing the MDB connections resulted in a significant decrease in intracranial pressure. Thus, these results indicated that muscular activation of the MDB may affect CSF circulation, suggesting a potential functional role of the MDB, and providing a new research perspective on CSF dynamics.

Humoral immunity at the brain borders in homeostasis.

The meninges encase the brain and spinal cord and house a variety of immune cells, including developing and mature B cells, and antibody-secreting plasma cells. In homeostasis, these cells localize around the dural venous sinuses, providing a defense 'zone' to protect the brain and spinal cord from blood-borne pathogens. Dural plasma cells predominantly secrete IgA antibodies, and some originate from the gastrointestinal tract, with the number and antibody isotype shaped by the gut microbiome. For developing B cells arriving from the adjacent bone marrow, the dura provides a site to tolerize against central nervous system antigens. In this review, we will discuss our current understanding of meningeal humoral immunity in homeostasis.

Quantitative evaluation of the regenerated dura mater in a decompressive skull trepanation model in rats / Evaluación cuantitativa de la duramadre regenerada en un modelo de perforación cranial descompresiva en ratas

SUMMARY: Regeneration of the dura mater following duraplasty using a collagen film, a chitosan film, or a combination of both with gelatin, was studied in a craniotomy and penetrating brain injury model in rats. Collagen autofluorescence in the regenerated dura mater was evaluated using confocal microscopy with excitation at λem = 488 nm and λem = 543 nm. An increase in regeneration of the extracellular matrix of connective tissue and an increase in matrix fluorescence were detected at 6 weeks after duraplasty. The major contributors to dura mater regeneration were collagen films, chitosan plus gelatin-based films, and, to a much lesser extent, chitosan-based films. By using autofluorescence densitometry of extracellular matrix, the authors were able to quantify the degree of connective tissue regeneration in the dura mater following duraplasty.

RESUMEN: Se estudió la regeneración de la duramadre después de una duraplastía utilizando una lámina de colágeno, una lamina de quitosano o una combinación de ambas con gelatina en un modelo de craneotomía y lesión cerebral en ratas. La autofluorescencia del colágeno en la duramadre regenerada se evaluó mediante microscopía confocal con excitación a λem = 488 nm y λem = 543 nm. Se observó un aumento en la regeneración de la matriz extracelular del tejido conectivo y un aumento en la fluorescencia de la matriz a las 6 semanas después de la duraplastía. Se observe un efecto significativo en la regeneración de la duramadre con las láminas de colágeno, las láminas en base de quitosano más gelatina y, en un menor grado, las láminas a base de quitosano. Mediante el uso de densitometría de autofluorescencia de la matriz extracelular, los autores lograron cuantificar el grado de regenera- ción del tejido conectivo en la duramadre después de la duraplastía.

A specialized myodural bridge named occipital-dural muscle in the narrow-ridged finless porpoise (Neophocaena asiaeorientalis).

A dense bridge-like tissue named the myodural bridge (MDB) connecting the suboccipital muscles to the spinal dura mater was originally discovered in humans. However, recent animal studies have revealed that the MDB appears to be an evolutionarily conserved anatomic structure which may have significant physiological functions. Our previous investigations have confirmed the existence of the MDB in finless porpoises. The present authors conducted research to expound on the specificity of the MDB in the porpoise Neophocana asiaeorientalis (N.asiaeorientalis). Five carcasses of N.asiaeorientalis, with formalin fixation, were used for the present study. Two of the carcasses were used for head and neck CT scanning, three-dimensional reconstructions, and gross dissection of the suboccipital region. Another carcass was used for a P45 plastination study. Also, a carcass was used for a histological analysis of the suboccipital region and also one was used for a Scanning Electron Microscopy study. The results revealed that the MDB of the N.asiaeorientalis is actually an independent muscle originating from the caudal border of the occiput, passing through the posterior atlanto-occipital interspace, and then attaches to the cervical spinal dura mater. Thus the so called MDB of the N.asiaeorientalis is actually an independent and uniquely specialized muscle. Based on the origin and insertion of this muscle, the present authors name it the 'Occipital-Dural Muscle'. It appears that the direct pull of this muscle on the cervical spinal dura mater may affect the circulation of the cerebrospinal fluid by altering the volume of the subarachnoid space via a pumping action.

Recognition and differentiation of dural puncture click sensation: A subjective and objective prospective study of dural puncture forces using fine-gauge spinal needles.

BACKGROUND: We hypothesized that the click perceived when puncturing the dura-arachnoid with fine-gauge spinal needles can be subjectively identified, and investigated whether it may be distinguishable among different needle types. METHODS: Subjective and objective evaluations were performed. First, physicians punctured the polyamide film or porcine dura mater (n = 70 and n = 20, respectively) with seven types of spinal needles and numerically evaluated the perceived click sensations. Using an 11-point numerical rating scale (from "0" for "no click sensation" to "10" for "the strongest click perceived") data, subjective differentiation among needle types was assessed. Second, in the objective part of the study, total forces elicited by polyamide film or porcine dura mater punctures with each needle were measured using a biomechanical testing device, and load-displacement curves evaluated. Third, the results of subjective and objective evaluations were compared. RESULTS: All participants recognized the click and could discriminate among needles of different tip shape. The load-displacement curves for polyamide film and porcine dura mater were similar and needle-specific. The subjective numerical rating scale values corresponded well with the objectively measured changes in total forces (R2 = 0.862 and R2 = 0.881 for polyamide film and porcine dura mater, respectively), indicating that an increase in the largest drop in total force value of 0.30 N or 0.21 N would produce an increase of numerical rating scale value of 1 for polyamide film and porcine dura mater, respectively. CONCLUSIONS: We provide an objective proof of the click sensation felt upon dural puncture using different fine-gauge spinal needles. Click recognition could be used as an additional indicator of successful spinal puncture.

Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma.

The meninges are a membranous structure enveloping the central nervous system (CNS) that host a rich repertoire of immune cells mediating CNS immune surveillance. Here, we report that the mouse meninges contain a pool of monocytes and neutrophils supplied not from the blood but by adjacent skull and vertebral bone marrow. Under pathological conditions, including spinal cord injury and neuroinflammation, CNS-infiltrating myeloid cells can originate from brain borders and display transcriptional signatures distinct from their blood-derived counterparts. Thus, CNS borders are populated by myeloid cells from adjacent bone marrow niches, strategically placed to supply innate immune cells under homeostatic and pathological conditions. These findings call for a reinterpretation of immune-cell infiltration into the CNS during injury and autoimmunity and may inform future therapeutic approaches that harness meningeal immune cells.

A double-layer dura mater based on poly(caprolactone-co-lactide) film and polyurethane sponge: preparation, characterization, and biodegradation study.

Synthetic, biodegradable polymers hold great potential in dura mater substitution. In this study, a dura mater-mimetic double-layer film@sponge composite was developed. The composite contains a poly(caprolactone-co-lactide) (PCLA) film and polyurethane (PU) sponge, which simulates the hard and soft layers of dura mater, respectively. PCLA films were prepared by a solution-casting method and showed excellent mechanical properties and tolerance to water. PU sponge was hydrophilic and had a high water-absorption rate (about 500%). The double-layer composite (film@sponge) integrated the good mechanical properties of the films and the good water absorption of the sponge. The excellent biocompatibility and biodegradability of the PCLA film@PU sponge composites were verified by in vitro degradation and cytotoxicity study and the in vivo implantation in the back of rats. Importantly, the film@sponge composite had a suitable degradation rate and good biocompatibility, holding potential in the field of dural repair.

Functional characterization of the dural sinuses as a neuroimmune interface.

Despite the established dogma of central nervous system (CNS) immune privilege, neuroimmune interactions play an active role in diverse neurological disorders. However, the precise mechanisms underlying CNS immune surveillance remain elusive; particularly, the anatomical sites where peripheral adaptive immunity can sample CNS-derived antigens and the cellular and molecular mediators orchestrating this surveillance. Here, we demonstrate that CNS-derived antigens in the cerebrospinal fluid (CSF) accumulate around the dural sinuses, are captured by local antigen-presenting cells, and are presented to patrolling T cells. This surveillance is enabled by endothelial and mural cells forming the sinus stromal niche. T cell recognition of CSF-derived antigens at this site promoted tissue resident phenotypes and effector functions within the dural meninges. These findings highlight the critical role of dural sinuses as a neuroimmune interface, where brain antigens are surveyed under steady-state conditions, and shed light on age-related dysfunction and neuroinflammatory attack in animal models of multiple sclerosis.

Three-dimensional finite element analysis of the dural folds and the human skull under head acceleration.

Bone and collagen fiber architecture adapt to external mechanical loads. In humans, due to the low insertion of the temporal muscle, mastication does not lead to a physiological loading of the calvaria. Forces applied to the skull by the dural folds can lead to compressive stresses in the calvaria. To investigate the relationship between mechanical loads and form in the skull and its membranes, in a finite element three-dimensional model of the human skull, loads due to head acceleration in daily activities are applied to the falx cerebri and the tentorium cerebelli. The dural folds are modeled as membranes. The stress paths in the dural folds correlate with anatomical fiber direction. Head accelerations of 9 g lead to compressive stress in the calvaria. Finite element analysis of the falx cerebri and the tentorium cerebelli can be used to study the influence of mechanical stresses on the ossification of the dural folds and their impact on calvarial growth. This study presents an example of functional loading of bone by fibrous membranes and describes a possible mechanism by which Wolff's law works on the bone of the calvaria creating evolutionarily beneficial lightweight constructions.

Responses of spinal trigeminal neurons to noxious stimulation of paranasal cavities - a rat model of rhinosinusitis headache.

BACKGROUND: The pathophysiology of headaches associated with rhinosinusitis is poorly known. Since the generation of headaches is thought to be linked to the activation of intracranial afferents, we used an animal model to characterise spinal trigeminal neurons with nociceptive input from the dura mater and paranasal sinuses. METHODS: In isoflurane anaesthetised rats, extracellular recordings were made from neurons in the spinal trigeminal nucleus with afferent input from the exposed frontal dura mater. Dural and facial receptive fields were mapped and the paranasal cavities below the thinned nasal bone were stimulated by sequential application of synthetic interstitial fluid, 40 mM potassium chloride, 100 µM bradykinin, 1% ethanol (vehicle) and 100 µm capsaicin. RESULTS: Twenty-five neurons with input from the frontal dura mater and responses to chemical stimulation of the paranasal cavities were identified. Some of these neurons had additional receptive fields in the parietal dura, most of them in the face. The administration of synthetic interstitial fluid, potassium chloride and ethanol was not followed by significant changes in activity, but bradykinin provoked a cluster of action potentials in 20 and capsaicin in 23 neurons. CONCLUSION: Specific spinal trigeminal neurons with afferent input from the cranial dura mater respond to stimulation of paranasal cavities with noxious agents like bradykinin and capsaicin. This pattern of activation may be due to convergent input of trigeminal afferents that innervate dura mater and nasal cavities and project to spinal trigeminal neurons, which could explain the genesis of headaches due to disorders of paranasal sinuses.

Mechanical Properties of the Cranial Meninges: A Systematic Review.

The meninges are membranous tissues that are pivotal in maintaining homeostasis of the central nervous system. Despite the importance of the cranial meninges in nervous system physiology and in head injury mechanics, our knowledge of the tissues' mechanical behavior and structural composition is limited. This systematic review analyzes the existing literature on the mechanical properties of the meningeal tissues. Publications were identified from a search of Scopus, Academic Search Complete, and Web of Science and screened for eligibility according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review details the wide range of testing techniques employed to date and the significant variability in the observed experimental findings. Our findings identify many gaps in the current literature that can serve as a guide for future work for meningeal mechanics investigators. The review identifies no peer-reviewed mechanical data on the falx and tentorium tissues, both of which have been identified as key structures in influencing brain injury mechanics. A dearth of mechanical data for the pia-arachnoid complex also was identified (no experimental mechanics studies on the human pia-arachnoid complex were identified), which is desirable for biofidelic modeling of human head injuries. Finally, this review provides recommendations on how experiments can be conducted to allow for standardization of test methodologies, enabling simplified comparisons and conclusions on meningeal mechanics.

Dynamic changes in longitudinal stretching of the spinal cord in thoracic spine: Focus on the spinal cord occupation rate of dural sac.

OBJECTIVES: This study aimed to evaluate the anteroposterior diameters and cross-sectional areas of the dural sac and spinal cord in the thoracic spine, to elucidate the spinal cord occupation rate of the dural sac in these dynamic changes for each level using multidetector-row computed tomography (MDCT). PATIENTS AND METHODS: Fifty patients with cervical or lumbar spinal disease were prospectively enrolled. After preoperative myelography, MDCT was performed at maximum passive flexion and extension. The anteroposterior diameter and cross-sectional area of the dural sac and spinal cord in the axial plane and the thoracic spinal cord length in the sagittal plane were measured. The spinal cord occupation rate in the dural sac was calculated. RESULTS: The spinal cord occupation rate of the dural sac in anteroposterior diameter was lower on flexion than on extension, with significant differences from the T1/T2 to T11/T12 levels (p < 0.0001). The spinal cord occupation rate of the dural sac in cross-sectional area was lower on flexion than on extension, with significant differences except from T3/T4 to T6/T7 levels (p < 0.01). There was a bimodal increase in the occupation rate with elevations at the cervicothoracic junction and thoracolumbar junction. The thoracic spinal cord length on flexion was significantly longer than that on extension (p < 0.0001). CONCLUSIONS: The spinal cord occupation rate of the dural sac was lower on flexion than on extension, despite thoracic spine being considered a rigid region. The dynamic changes in longitudinal stretching and shrinkage of the spinal cord affected the occupation rate.

Fabrication and Properties of a Biomimetic Dura Matter Substitute Based on Stereocomplex Poly(Lactic Acid) Nanofibers.

BACKGROUND: Duraplasty is one of the most critical issues in neurosurgical procedures because the defect of dura matter will cause many complications. Electrospinning can mimic the 3D structure of the natural extracellular matrix whose structure is similar to that of dura matter. Poly(L-lactic acid) (PLLA) has been used to fabricate dura matter substitutes and showed compatibility to dural tissue. However, the mechanical properties of the PLLA substitute cannot match the mechanical properties of the human dura mater. METHODS AND RESULTS: We prepared stereocomplex nanofiber membranes based on enantiomeric poly(lactic acid) and poly(D-lactic acid)-grafted tetracalcium phosphate via electrospinning. X-ray diffraction results showed the formation of stereocomplex crystallites (SC) in the composite nanofiber membranes. Scanning electron microscope observation images showed that composites nanofibers with higher SC formation can keep its original morphologies after heat treatment, suggesting the heat resistance of composite nanofiber membranes. Differential scanning calorimeter tests confirmed that the melting temperature of composite nanofiber membranes was approximately 222°C, higher than that of PLLA. Tensile testing indicated that the ultimate tensile strength and the elongation break of the stereocomplex nanofiber membranes were close to human dura matter. In vitro cytotoxicity studies proved that the stereocomplex nanofiber membranes were non-toxic. The neuron-like differentiation of marrow stem cells on the stereocomplex nanofiber membranes indicated its neuron compatibility. CONCLUSION: The stereocomplex nanofiber membranes have the potential to serve as a dura mater substitute.

Bilaminar Structure of the Human Optic Nerve Sheath.

PURPOSE/AIM: We aimed to characterize the connective tissue microanatomy, elastin abundance, and fiber orientation in the human optic nerve sheath, also known as the optic nerve dura mater, for correlation with its biomechanical properties. MATERIALS AND METHODS: Seven whole human orbits aged 4-93 years, and five isolated human optic nerve sheaths aged 26-75 years were formalin fixed, paraffin embedded, coronally sectioned, stained by Masson trichrome and van Gieson's elastin methods, and analyzed quantitatively for elastin fiber abundance and orientation. Elastin area fraction was defined as area stained for elastin divided by total area. RESULTS: While unilaminar in children, the adult ON sheath exhibited distinct inner and outer layers. Collagen was denser and more compact in the inner layer. Elastin area fraction was significantly greater at 6.0 ± 0.4% (standard error of mean) in the inner than outer layer at 3.6 ± 0.4% (P < 10-5). Elastin fibers had three predominant orientations: longitudinal, diagonal, and circumferential. Of circumferential fibers, 63 ± 4.7% were in the inner and 37 ± 4.7% in the outer layer (P < 10-4). Longitudinal and diagonal fibers were uniformly distributed in both layers. Elastin density and sheath thickness increased significantly with age (P < .01). CONCLUSIONS: The adult human optic nerve sheath is bilaminar, with each layer containing elastin fibers oriented in multiple directions consistent with isotropic properties. Differences in laminar elastin density and orientation may reflect greater tensile loading in the inner than in the outer layer.