Pia Arachnoid Research Articles

Adhesive arachnoiditis, subarachnoid hemorrhage, and intradural extramedullary thoracic cavernoma: illustrative case.

Spinal arachnoiditis can result from various factors, including spinal subarachnoid hemorrhage (sSAH). In this paper, the authors describe a case of intradural extramedullary cavernoma with an initial presentation of subarachnoid hemorrhage leading to multilevel spinal arachnoiditis to discuss the pathophysiology and optimal treatment strategy. Spinal intradural extramedullary cavernoma manifesting with sSAH is a rare clinical presentation; therefore, there is no clear strategy for the management of sSAH. Spinal arachnoiditis is a result of chronic inflammation of the pia arachnoid layer due to hematomyelia. No effective treatment that interrupts this inflammatory cascade and would also prevent the development of spinal arachnoiditis has been described to date. Lumbar drainage could aid in sSAH management, relieve spinal cord compression, and restore the normal spinal cerebrospinal fluid circulation gradient. It could help to clear the blood degradation products rapidly and prevent early inflammatory arachnoiditis development. Mini-invasive intrathecal endoscopic adhesiolysis appears to be a reasonable approach for reducing the risk of aggravating spinal arachnoiditis with a mechanical-surgical stimulus. Whether a conservative approach should be applied in these patients with mild myelopathy symptoms is still debatable.

Ex-vivo quantification of ovine pia arachnoid complex biomechanical properties under uniaxial tension

BackgroundThe pia arachnoid complex (PAC) is a cerebrospinal fluid-filled tissue conglomerate that surrounds the brain and spinal cord. Pia mater adheres directly to the surface of the brain while the arachnoid mater adheres to the deep surface of the dura mater. Collagen fibers, known as subarachnoid trabeculae (SAT) fibers, and microvascular structure lie intermediately to the pia and arachnoid meninges. Due to its structural role, alterations to the biomechanical properties of the PAC may change surface stress loading in traumatic brain injury (TBI) caused by sub-concussive hits. The aim of this study was to quantify the mechanical and morphological properties of ovine PAC.MethodsOvine brain samples (n = 10) were removed from the skull and tissue was harvested within 30 min post-mortem. To access the PAC, ovine skulls were split medially from the occipital region down the nasal bone on the superior and inferior aspects of the skull. A template was used to remove arachnoid samples from the left and right sides of the frontal and occipital regions of the brain. 10 ex-vivo samples were tested with uniaxial tension at 2 mm s−1, average strain rate of 0.59 s−1, until failure at < 5 h post extraction. The force and displacement data were acquired at 100 Hz. PAC tissue collagen fiber microstructure was characterized using second-harmonic generation (SHG) imaging on a subset of n = 4 stained tissue samples. To differentiate transverse blood vessels from SAT by visualization of cell nuclei and endothelial cells, samples were stained with DAPI and anti-von Willebrand Factor, respectively. The Mooney-Rivlin model for average stress–strain curve fit was used to model PAC material properties.ResultsThe elastic modulus, ultimate stress, and ultimate strain were found to be 7.7 ± 3.0, 2.7 ± 0.76 MPa, and 0.60 ± 0.13, respectively. No statistical significance was found across brain dissection locations in terms of biomechanical properties. SHG images were post-processed to obtain average SAT fiber intersection density, concentration, porosity, tortuosity, segment length, orientation, radial counts, and diameter as 0.23, 26.14, 73.86%, 1.07 ± 0.28, 17.33 ± 15.25 µm, 84.66 ± 49.18°, 8.15%, 3.46 ± 1.62 µm, respectively.ConclusionFor the sizes, strain, and strain rates tested, our results suggest that ovine PAC mechanical behavior is isotropic, and that the Mooney-Rivlin model is an appropriate curve-fitting constitutive equation for obtaining material parameters of PAC tissues.

Epidemiological profile of confirmed meningitis cases reported in the state of Ceará from 2014 to 2018

Meningitis is an inflammatory process that affects the brain membranes (pia mater and arachnoid), and cerebrospinal fluid (CSF). Such a process can be caused by viruses and bacteria. The aim of this study was to analyze the epidemiological profile of cases of meningitis in the state of Ceará, reported from 2014 to 2018. This is a cross-sectional, exploratory study that outlined a quantitative and descriptive study on cases of meningitis in the state of Ceará. Ceará, retrospectively, from 2014 to 2018. Data from the Department of Informatics of SUS, DATASUS, were used. Of the 1710 reported cases of meningitis, the highest prevalence was in the 20-39 age group and the 40-59 age group, 32.0% and 20.6%, respectively. Males account for 62% of confirmations. 1398 occur in the state capital, Fortaleza, being of majority expression. The diagnostic test with the highest number of confirmations is the chemocytological test.

Isolation and Immunofluorescent Staining of Fresh Rat Pia-Arachnoid Complex Tissue for Micromechanical Characterization.

In this article, we describe a protocol for the isolation and staining of fresh tissue of the inner rat meningeal layers, or pia-arachnoid complex (PAC). The PAC is believed to act as a mechanical damper offering a fundamental layer of protection against brain injury; however, its overall mechanical properties are still rather unexplored. In order to perform micromechanical measurements on the PAC, the tissue must be extracted and characterized while maintaining its native mechanical properties (i.e., avoiding any chemical or physical modification that could alter it). In light of this need, we developed a protocol for the immunofluorescent staining of fresh PAC tissue that does not require any fixation or permeabilization step. This approach will allow researchers to investigate important properties of the anatomy of ex vivo PAC tissue while at the same time offering a platform for the mechanical analysis of this complex material. © 2019 by John Wiley & Sons, Inc. Basic Protocol 1: Isolation of fresh rat pia-arachnoid complex tissue Basic Protocol 2: Fresh immunofluorescent staining of rat pia-arachnoid complex tissue Alternate Protocol: Adhesion of pia-arachnoid complex tissue to glass slides for micromechanical characterization.

Histological study of meningeal structures associated with lower cranial nerves through jugular foramen with Mimics software

Objective To study histological and anatomical features of pia mater, arachnoid mater, dura mater and myelin sheath of lower cranial nerves through jugular foramen. Methods Nine (18 sides) fetal full-term cadaveric heads (28-36 weeks) were randomly divided into 3 groups and each group included 6 sides. The sagittal, horizontal and coronal plane slices were manufactured containing lower cranial nerves through jugular foramen, which were fixed, dehydrated, wax dipped, embedded, sliced and stained by the Masson method. The starting and ending positions as well as distribution of related pia mater, arachnoid mater, dura mater and myelin sheath were observed under surgical microscope. The meningeal structures underwent three-dimensional reconstruction using the software of Mimics 10.0. Results The lower cranial nerves went though jugular foramen, where dura mater, arachnoid mater, pia mater and the transitional zone between central myelin sheath and peripheral myelin sheath were observed. Dura mater included meningeal layer and periosteal layer, formed a dura pocket at jugular foramen and a dura fold above the inner orifice. Arachnoid mater extended to superior ganglia and looked like sleeves which disappeared past ganglia. Pia mater clung to medulla oblongata where nerve roots were and disappeared after that. Conclusions The microanatomy of meningeal structures of lower cranial nerves could be visually demonstrated with Mimics 10.0 software, which provides anatomical information for related disorders and operations based on layers and interfaces of meningeal structures. Key words: Neuroanatomy; Jugular foramen; Lower cranial nerves; Meningeal structure; Histology; Mimics 10.0 software

Three-Dimensional Reconstruction of the Topographical Cerebral Surface Anatomy for Presurgical Planning With Free OsiriX Software

During surgery for intrinsic brain lesions, it is important to distinguish the pathological gyrus from the surrounding normal sulci and gyri. This task is usually tedious because of the pia-arachnoid membranes with their arterial and venous complexes that obscure the underlying anatomy. Moreover, most tumors grow in the white matter without initially distorting the cortical anatomy, making their direct visualization more difficult. To create and evaluate a simple and free surgical planning tool to simulate the anatomy of the surgical field with and without vessels. We used free computer software (OsiriX Medical Imaging Software) that allowed us to create 3-dimensional reconstructions of the cerebral surface with and without cortical vessels. These reconstructions made use of magnetic resonance images from 51 patients with neocortical supratentorial lesions operated on over a period of 21 months (June 2011 to February 2013). The 3-dimensional (3-D) anatomic images were compared with the true surgical view to evaluate their accuracy. In all patients, the landmarks determined by 3-D reconstruction were cross-checked during surgery with high-resolution ultrasonography; in select cases, they were also checked with indocyanine green videoangiography. The reconstructed neurovascular structures were confirmed intraoperatively in all patients. We found this technique to be extremely useful in achieving pure lesionectomy, as it defines tumor's borders precisely. A 3-D reconstruction of the cortical surface can be easily created with free OsiriX software. This technique helps the surgeon perfect the mentally created 3-D picture of the tumor location to carry out cleaner, safer surgeries.

Constitutive Modeling of Pia–Arachnoid Complex

The pia-arachnoid complex (PAC) covering the brain plays an important role in the mechanical response of the brain during impact or inertial loading. Recent studies have revealed the complicated material behavior of the PAC. In this study, the nonlinear viscoelastic, transversely isotropic material properties of the PAC were modeled as Mooney-Rivlin ground substance with collagen fibers strengthening within the meningeal plane through an exponential model. The material constants needed were determined using experimental data from in-plane tension, normal traction, and shear tests conducted on bovine specimens. Results from this study provide essential information to properly model the PAC membrane, an important component in the skull/brain interface, in a computational brain model. Such an improved representation of the skull/brain interface will enhance the accuracy of finite element models used in brain injury mechanism studies under various loading conditions.

Optic Nerve Sheath Fenestration—Indications and Techniques

The optic nerve is a white matter tract of the brain and its sheath is composed of pia mater, arachnoid mater, and dura mater. The subarachnoid space (SAS) of the optic nerve sheath, which contains cerebrospinal fluid, is contiguous with the SAS of the brain. Elevated intracranial pressure is transmitted to the optic nerve head through the SAS resulting in papilledema. Optic nerve sheath fenestration (ONSF) can be an effective surgical technique to preserve vision in patients with progressive optic neuropathy due to papilledema caused by idiopathic intracranial hypertension (IIH); however, a dreaded complication of ONSF is visual loss. This article will discuss the rationale, indications, and complications of ONSF. A variety of surgical techniques can be employed to perform an ONSF. In particular, the medial transconjuctival approach will be highlighted.

Mechanical properties of bovine pia–arachnoid complex in shear

Traumatic brain injury (TBI) has become a major public health and socioeconomic problem that affects 1.5 million Americans annually. Finite element methods have been widely used to investigate TBI mechanisms. The pia–arachnoid complex (PAC) covering the brain plays an important role in the mechanical response of the brain during impact or inertial loading. Existing finite element brain models have tended to oversimplify the response of the PAC due to a lack of accurately defined material properties of this structure, possibly resulting in a loss of accuracy in the model predictions. The objectives of this study were to experimentally determine the material properties of the PAC under shear loading. Bovine PAC was selected in the current study in view of its availability and comparability with previous studies. Tangential shear tests were conducted at 0.8, 7.3, and 72 s −1. The mean shear moduli were 11.73, 20.04, and 22.37 kPa at the three strain rates tested. The ultimate stress, at the three strain rates, was 9.21, 17.01, and 22.26 kPa, while the ultimate strain was 1.52, 1.58, and 1.81. Results from the current study provide essential information to properly model the PAC membrane, an important component in the skull/brain interface, in a computational model of the human/animal head. Such an improved representation of the in vivo skull/brain interface will enhance future studies investigating brain injury mechanisms under various loading conditions.

BASIC SCIENCE

Cortical spreading depression (CSD) is a propagating wave of neuronal and glial depolarization and has been implicated in disorders of neurovascular regulation such as stroke, head trauma, and migraine. In this study, we found that CSD alters blood‐brain barrier (BBB) permeability by activating brain MMPs. Beginning at 3 to 6 hours, MMP‐9 levels increased within cortex ipsilateral to the CSD, reaching a maximum at 24 hours and persisting for at least 48 hours. Gelatinolytic activity was detected earliest within the matrix of cortical blood vessels and later within neurons and pia arachnoid (&gt; or = 3 hours), particularly within piriform cortex; this activity was suppressed by injection of the metalloprotease inhibitor GM6001 or in vitro by the addition of a zinc chelator (1,10‐phenanthroline). At 3 to 24 hours, immunoreactive laminin, endothelial barrier antigen, and zona occludens‐1 diminished in the ipsilateral cortex, suggesting that CSD altered proteins critical to the integrity of the BBB. At 3 hours after CSD, plasma protein leakage and brain edema developed contemporaneously. Albumin leakage was suppressed by the administration of GM6001. Protein leakage was not detected in MMP‐9‐null mice, implicating the MMP‐9 isoform in barrier disruption. We conclude that intense neuronal and glial depolarization initiates a cascade that disrupts the BBB via an MMP‐9‐dependent mechanism. Comment: This study is from the lab of Professor Michael Moskowitz at Harvard. Dr. Moskowitz feels that the membrane metalloproteinases (MMPs) play a key role in the breakdown of the blood brain barrier in cortical spreading depression, and thus are central to the genesis of aura and migraine. He plans ongoing studies on the MMPs, which may provide potential new targets for new medications for migraine.—Stewart J. Tepper

Biomechanics of the spinal cord

Although the spinal cord has a vital role in the function of the central nervous system, there have been relatively few investigations into its biomechanical and physical properties. Therefore, knowledge is comparatively limited in this regard. A definition of the basic physical behavior of the spinal cord and its response to stress provides valuable insight into the pathophysiology and the potential management strategies of its disease states. The spinal cord is a dynamic structure contained within the bony spinal canal, which while rigid, undergoes significant geometric changes with the physiologic movements of flexion, extension, axial rotation, and lateral bending. The unique physical properties of the spinal cord allow it to adapt to the physiologic and anatomic changes in the length and cross-sectional area of the spinal canal, while maintaining neurological function. However, alterations of the spinal canal secondary to trauma, neoplasm, deformity, instability, or the degenerative process can generate stresses on the spinal cord that can lead to pathologic dysfunction. In addition, alterations of the mechanical behavior of the spinal cord, such as that associated with spinal cord tethering, can also generate stresses that produce dysfunction. The onset, duration, and intensity of these stresses define the magnitude and potential reversibility of the spinal cord dysfunction. Within the confines of the bony canal, the spinal cord is invested in the soft-tissue structures of the pia arachnoid and dura mater, and the dentate ligament, epidural fat, and veins. It is bathed in cerebrospinal fluid. These structures also contribute to the biomechanical and physical behavior of the spinal cord.

Cortical spreading depression activates and upregulates MMP-9.

Cortical spreading depression (CSD) is a propagating wave of neuronal and glial depolarization and has been implicated in disorders of neurovascular regulation such as stroke, head trauma, and migraine. In this study, we found that CSD alters blood-brain barrier (BBB) permeability by activating brain MMPs. Beginning at 3-6 hours, MMP-9 levels increased within cortex ipsilateral to the CSD, reaching a maximum at 24 hours and persisting for at least 48 hours. Gelatinolytic activity was detected earliest within the matrix of cortical blood vessels and later within neurons and pia arachnoid (> or =3 hours), particularly within piriform cortex; this activity was suppressed by injection of the metalloprotease inhibitor GM6001 or in vitro by the addition of a zinc chelator (1,10-phenanthroline). At 3-24 hours, immunoreactive laminin, endothelial barrier antigen, and zona occludens-1 diminished in the ipsilateral cortex, suggesting that CSD altered proteins critical to the integrity of the BBB. At 3 hours after CSD, plasma protein leakage and brain edema developed contemporaneously. Albumin leakage was suppressed by the administration of GM6001. Protein leakage was not detected in MMP-9-null mice, implicating the MMP-9 isoform in barrier disruption. We conclude that intense neuronal and glial depolarization initiates a cascade that disrupts the BBB via an MMP-9-dependent mechanism.

Cholinergic innervation of pial arteries in senescent rats: an immunohistochemical study

Perivascular acetylcholine (ACh)-immunoreactive nerve fibres were demonstrated in basilar and middle cerebral arteries, in pial arteries and arterioles and in intracerebral arteries of male Fisher 344 rats of 6 months (young), 15 months (adult) and 22 months (senescent). Analysis included whole mounts of basilar and middle cerebral arteries, of pial arteries and sections of brain including pia-arachnoid membrane to demonstrate the localization of nerve fibres throughout the wall of pial and of intracerebral arteries. ACh-immunoreactive nerve fibres were demonstrated by indirect immunohistochemistry using a polyclonal anti-ACh antibody and their relative density was quantified. Perivascular ACh-immunoreactive nerve fibres were located in basilar and middle cerebral arteries, in pial arteries and arterioles and in intracerebral arteries. These fibres were found in the adventitia and adventitia–media border with a higher density in pial rather than in intracerebral arteries. A decrease of ACh-immunoreactive nerve fibres was observed both in pial and intracerebral arteries of adult or senescent rats compared to younger cohorts. The direct demonstration of ACh-immunoreactive nerve fibres in the cerebrovascular tree may contribute to evaluate the influence of experimental and pathological conditions on cerebrovascular cholinergic neuroeffector mechanisms, including a role of cholinergic innervation in the pathophysiology of cerebrovascular disease of the elderly.

Dopamine D1-D5 receptor protein immunohistochemistry in dog pial arteries

The localization of dopamine D1-D5 receptor protein was investigated in different sized dog pial arteries. This was done to further understand the pathophysiology of cerebrovascular dopaminergic system in migraine. The study was performed in sections of dog brain including the pia-arachnoid membrane, which were processed for indirect immunohistochemistry using antibodies raised against dopamine D1-D5 receptor protein. A faint dopamine D1 receptor protein immunoreactivity was observed in smooth muscle of the tunica media of different sized pial arteries. Dopamine D2 receptor protein immunoreactivity was located in the adventitia and adventitia-media border of pial arteries. In the same area tyrosine hydroxylase immunoreactive nerve fibers were found. No dopamine D3 receptor immunoreactivity was detectable in dog pial arteries. A faint dopamine D4 receptor protein immunoreactivity was observed in dog pial arteries, with a localization similar to that of D2 receptor protein. A moderate dopamine D5 receptor protein immunostaining was observed in smooth muscle of the tunica media. These findings indicate that dog pial arteries express dopamine D1-like (D1 and D5) and D2-like (D2 and D4) receptor subtypes and display, respectively, a muscular (post-junctional) and probably prejunctional localization. These results, the first analysis of dopamine D1-D5 receptor subtype distribution in the cerebrovascular tree, suggest that dopamine is involved in the regulation of cerebral circulation. These finding may help evaluate the role of cerebrovascular dopaminergic mechanisms in the pathogenesis of migraine.

Anatomy of Soft Tissues of the Spinal Canal

Background and Objectives. Important issues regarding the spread of solutions in the epidural space and the anatomy of the site of action of spinal and epidural injections are unresolved. However, the detailed anatomy of the spinal canal has been incompletely determined. We therefore examined the microscopic anatomy of the spinal canal soft tissues, including relationships to the canal walls. Methods. Whole mounts were prepared of decalcified vertebral columns with undisturbed contents from three adult humans. Similar material was prepared from a macaque and baboon immediately on death to control for artifact of tissue change after death. Other tissues examined included nerve root and proximal spinal nerve complex and dorsal epidural fat obtained during surgery. Slides were examined by light microscopy at magnifications of 10-40×. Results. There is no fibrous tissue in the epidural space. The epidural fat is composed of uniform cells enclosed in a fine membrane. The dorsal fat is only attached to the canal wall in the dorsal midline and is often tenuously attached to the dura. The dura is joined to the canal wall only ventrally at the discs. Veins are evident predominantly in the ventral epidural space. Nerve roots are composed of multiple fascicles which disperse as they approach the dorsal root ganglion. An envelope of arachnoid encloses the roots near the site of exit from the dura. Conclusions. These features of the fat explain its semifluid consistency. Lack of substantial attachments to the dura facilitate movement of the dura relative to the canal wall and allow distribution of injected solution. Fibrous barriers are an unlikely explanation for asymmetric epidural anesthesia, but the midline fat could impede solution spread. Details of nerve-root structure and their envelope of pia-arachnoid membrane may be relevant to anesthetic action.

Anatomy of soft tissues of the spinal canal

Background and Objectives. Important issues regarding the spread of solutions in the epidural space and the anatomy of the site of action of spinal and epidural injections are unresolved. However, the detailed anatomy of the spinal canal has been incompletely determined. We therefore examined the microscopic anatomy of the spinal canal soft tissues, including relationships to the canal walls. Methods. Whole mounts were prepared of decalcified vertebral columns with undisturbed contents from three adult humans. Similar material was prepared from a macaque and baboon immediately on death to control for artifact of tissue change after death. Other tissues examined included nerve root and proximal spinal nerve complex and dorsal epidural fat obtained during surgery. Slides were examined by light microscopy at magnifications of 10–40×. Results. There is no fibrous tissue in the epidural space. The epidural fat is composed of uniform cells enclosed in a fine membrane. The dorsal fat is only attached to the canal wall in the dorsal midline and is often tenuously attached to the dura. The dura is joined to the canal wall only ventrally at the discs. Veins are evident predominantly in the ventral epidural space. Nerve roots are composed of multiple fascicles which disperse as they approach the dorsal root ganglion. An envelope of arachnoid encloses the roots near the site of exit from the dura. Conclusions. These features of the fat explain its semifluid consistency. Lack of substantial attachments to the dura facilitate movement of the dura relative to the canal wall and allow distribution of injected solution. Fibrous barriers are an unlikely explanation for asymmetric epidural anesthesia, but the midline fat could impede solution spread. Details of nerve-root structure and their envelope of pia-arachnoid membrane may be relevant to anesthetic action.

The epidural potato − and beyond

Dr Tuckey's potato model for teaching epidural puncture deserves high praise. It is simple, portable and convincing to students at all stages, and in any language [1]. The model is also adaptable to demonstrating the loss-of-resistance-to-negative-pressure test (or ‘suck-and-see’ technique) that I have used exclusively as a safety measure for lumbar or thoracic subarachnoid puncture in humans, and for cisternal puncture in experimental animals [2]. This old and much neglected technique prevents accidental sequestration of any spinal injectate in the subdural space between the pia arachnoid and the dura mater − a nuisance that otherwise occurs in 5–10% of spinal injections [3, 4]. To adapt Dr Tuckey's model for subarachnoid puncture: 1Take a large, washed potato free of wrinkles. Slice in half, taking care to avoid cutting through an ‘eye’ dimple near the circumference of the cut surface. 2Dry the cut surface of the chosen half. 3Wrap a sheet of kitchen plastic film loosely over the cut and dried surface, and secure a gas-tight seal around the circumference with two or three tightly stretched rubber bands, leaving a very slight air pocket between the plastic film (representing the pia-arachnoid membrane) and the cut surface of the potato (representing the inner surface of the dura mater). 4Take a 4-cm 18-gauge hypodermic needle as an introducer and insert it into the butt end of the potato, aiming for the cut surface and advance a 25-gauge Whitacre needle through the introducer (clinically, a 27-gauge Whitacre needle is ideal but, for this artificial model, the stiffer 25-gauge is needed to overcome the more resistant texture of a raw potato). 5Remove the stilette and firmly attach an empty 2-ml syringe to ensure a gas-tight fit. 6Immerse the potato slant-wise in a glass of water and observe the cut surface of the potato. 7While advancing the Whitacre needle, distract the plunger of the attached syringe with middle finger and thumb while exerting counter pressure on the barrel rim with the extended forefinger, and retract the plunger to a volume of 1.75–2.0 ml. This will create a negative pressure of approximately − 600 mmHg, transmitted to the needle orifice [2]. 8Continue to advance the 25-gauge needle very carefully while applying vacuum and an assistant steadies the ‘dura’ until the needle orifice appears. At that instance, the transmitted vacuum ‘snaps’ the ‘pia-arachnoid’ onto the needle point, penetrating the ‘pia’ and collapsing the artefactual subdural space, as water spurts back into the vacuum syringe. 9The needle orifice has evaded the subdural space and is safely within the subarachnoid space. The specialty has waited a long time for a simple bench model to demonstrate the advantages of the ‘suck-and-see’ technique for subarachnoid puncture and its three intrinsic virtues of improved safety, efficacy and parsimony at all spinal levels from the cisterna magna downwards. Dr Tuckey's simple model makes a significant contribution to that educational goal.

Absence of neuronal and glial proteins in human and rat leptomeninges in situ

Human leptomeningeal (arachnoid and pia mater) cells in culture have been demonstrated in replicated studies to express typical neuronal proteins such as neurofilament protein and neuron-specific enolase. In addition, they can express glial fibrillary acidic protein. The present study examines the possibility that neuronal and glial proteins might be present in rat and human leptomeningeal cells in situ. The neuronal proteins 160 kDa and 200 kDa neurofilaments, neuron-specific enolase and microtubule-associated protein 2 were, however, not immunolocalized in either the pia mater or arachnoid. Glial fibrillary acidic protein and galactocerebroside were also not detected, while fibronectin and vimentin immunoreactivities were robust in all layers of the leptomeninges. Together with the previously reported expression of some neuronal and astroglial markers in cultured human leptomeninges, these observations suggest that culture alters the properties of leptomeningeal cells.

Localization of drug-metabolizing enzyme activities to blood-brain interfaces and circumventricular organs.

The brain, with the exception of the choroid plexuses and circumventricular organs, is partially protected from the invasion of blood-borne chemicals by the specific morphological properties of the cerebral micro-vessels, namely, the tight junctions of the blood-brain barrier. Recently, several enzymes that are primarily involved in hepatic drug metabolism have been shown to exist in the brain, albeit at relatively low specific activities. In the present study, the hypothesis that these enzymes are located primarily at blood-brain interfaces, where they form an "enzymatic barrier," is tested. By using microdissection techniques or a gradient-centrifugation isolation procedure, the activities of seven drug-metabolizing enzymes in isolated microvessels, choroid plexuses, meningeal membranes, and tissue from three circumventricular organs (the neural lobe of the hypophysis, pineal gland, and median eminence) were assayed. With two exceptions, the activities of these enzymes were higher in the three circumventricular organs and cerebral microvessel than in the cortex. Very high membrane-bound epoxide hydrolase and UDP-glucuronosyltransferase activities (approaching those in liver) and somewhat high 7-benzoxyresorufin-O-dealkylase and NADPH-cytochrome P-450 reductase activities were determined in the choroid plexuses. The pia-arachnoid membranes, but not the dura matter, displayed drug-metabolizing enzyme activities, notably that of epoxide hydrolase. The drug-metabolizing enzymes located at these nonparenchymal sites may function to protect brain tissue from harmful compounds.

Experimental evaluation of collagen sponge as a dural graft.

Early collagen products, when used as dural substitutes, promoted severe inflammatory responses and fell into disrepute. A more recent advance, collagen sponge, which is derived from bovine flexor tendons was used in this experimental study. Collagen sponge was surgically implanted as an onlay dural replacement graft following skull trephination and dural excision in 12 primates. Macroscopic, histological and electron-microscopical evaluations were performed at periods of 1, 3 and 9 months. This preliminary animal study indicated that collagen sponge is suitable to use as a graft since it does not induce any inflammatory response or adhesions in the absence of pia arachnoid injury. If forms an ideal scaffold for the early ingrowth of fibroblasts to effect dural repair.