Identification of direct connections between the dura and the brain.

The arachnoid barrier delineates the border between the central nervous system and dura mater. Although the arachnoid barrier creates a partition, communication between the central nervous system and the dura mater is crucial for waste clearance and immune surveillance1,2. How the arachnoid barrier balances separation and communication is poorly understood. Here, using transcriptomic data, we developed transgenic mice to examine specific anatomical structures that function as routes across the arachnoid barrier. Bridging veins create discontinuities where they cross the arachnoid barrier, forming structures that we termed arachnoid cuff exit (ACE) points. The openings that ACE points create allow the exchange of fluids and molecules between the subarachnoid space and the dura, enabling the drainage of cerebrospinal fluid and limited entry of molecules from the dura to the subarachnoid space. In healthy human volunteers, magnetic resonance imaging tracers transit along bridging veins in a similar manner to access the subarachnoid space. Notably, in neuroinflammatory conditions such as experimental autoimmune encephalomyelitis, ACE points also enable cellular trafficking, representing a route for immune cells to directly enter the subarachnoid space from the dura mater. Collectively, our results indicate that ACE points are a critical part of the anatomy of neuroimmune communication in both mice and humans that link the central nervous system with the dura and its immunological diversity and waste clearance systems.

Stuck on you: Meninges cellular crosstalk in development.

The spatial and temporal development of the brain, overlying meninges (fibroblasts, vasculature and immune cells) and calvarium are highly coordinated. In particular, the timing of meningeal fibroblasts into molecularly distinct pia, arachnoid and dura subtypes coincides with key developmental events in the brain and calvarium. Further, the meninges are positioned to influence development of adjacent structures and do so via depositing basement membrane and producing molecular cues to regulate brain and calvarial development. Here, we review the current knowledge of how meninges development aligns with events in the brain and calvarium and meningeal fibroblast "crosstalk" with these structures. We summarize outstanding questions and how the use of non-mammalian models to study the meninges will substantially advance the field of meninges biology.

Arachnoid and dural reflections.

The dura mater is the major gateway for accessing most extra-axial lesions and all intra-axial lesions of the central nervous system. It provides a protective barrier against external trauma, infections, and the spread of malignant cells. Knowledge of the anatomical details of dural reflections around various corners of the skull bases provides the neurosurgeon with confidence during transdural approaches. Such knowledge is indispensable for protection of neurovascular structures in the vicinity of these dural reflections. The same concept is applicable to arachnoid folds and reflections during intradural excursions to expose intra- and extra-axial lesions of the brain. Without a detailed understanding of arachnoid membranes and cisterns, the neurosurgeon cannot confidently navigate the deep corridors of the skull base while safely protecting neurovascular structures. This chapter covers the surgical anatomy of dural and arachnoid reflections applicable to microneurosurgical approaches to various regions of the skull base.

[A case of antiphospholipid syndrome associated with recurrent brain infarction and diffuse hypertrophy of the arachnoid membrane].

A 55-year-old man presented with recurrent brain infarction which had increased multifocally mainly in the cerebral white matter over the course of one year. Antibodies associated with antiphospholipid syndrome (APS) were initially negative. The patient was admitted to our department because of the thickened meninges shown on gadolinium enhanced brain MRI, mimicking hypertrophic pachymeningitis. However, blood and cerebrospinal fluid analysis revealed no significant inflammatory changes. On histopathological examination of the biopsied meninges, the arachnoid membrane was thickened with fibrosis, and arachnoidal microvessels were enlarged without significant inflammatory changes. The dura mater was not thickened, and no inflammation or microvessel enlargement were revealed. Finally, serum IgG anticardiolipin antibody testing was positive twice at an interval of more than 12 weeks, confirming the diagnosis of APS. Since initiating antithrombotic therapy with warfarin, brain infarction has not recurred. Without inflammation in the arachnoid membrane, the congestion of blood flow caused by thrombosis of microvessels in the arachnoid membrane might have increased the thickness of the arachnoid membrane.

Giant arachnoid granulation with a thrombosed dural arteriovenous fistula.

Arachnoid granulations are common incidentally detected small dural lesions which are usually asymptomatic and follow cerebrospinal fluid density/signal intensity on CT/MRI. Such lesions reaching a size of more than 1 cm are termed as giant arachnoid granulations (GAGs) which have been previously reported to cause venous hypertension and headaches. We report a case of GAG involving the proximal half of the superior sagittal sinus in a 45-year-old male patient which was associated with left temporal thrombosed dural arteriovenous fistula (AVF) whose thrombosed draining veins were seen converging towards the site of GAG. The patient presented with three episodes of generalised tonic-clonic seizures and improved with conservative treatment. No reports of such association of GAG with AVF is available in the literature, and we believe it could have occurred due to venous hypertension induced by GAG.

Drug Clearance from Cerebrospinal Fluid Mediated by Organic Anion Transporters 1 (Slc22a6) and 3 (Slc22a8) at Arachnoid Membrane of Rats.

Although arachnoid mater epithelial cells form the blood-arachnoid barrier (BAB), acting as a blood-CSF interface, it has been generally considered that the BAB is impermeable to water-soluble substances and plays a largely passive role. Here, we aimed to clarify the function of transporters at the BAB in regulating CSF clearance of water-soluble organic anion drugs based on quantitative targeted absolute proteomics (QTAP) and in vivo analyses. Protein expression levels of 61 molecules, including 19 ATP-binding-cassette (ABC) transporters and 32 solute-carrier (SLC) transporters, were measured in plasma membrane fraction of rat leptomeninges using QTAP. Thirty-three proteins were detected; others were under the quantification limits. Expression levels of multidrug resistance protein 1 (Mdr1a/P-gp/Abcb1a) and breast cancer resistance protein (Bcrp/Abcg2) were 16.6 and 3.27 fmol/µg protein (51.9- and 9.82-fold greater than in choroid plexus, respectively). Among those organic anion transporters detected only at leptomeninges, not choroid plexus, organic anion transporter 1 (oat1/Slc22a6) showed the greatest expression (2.73 fmol/µg protein). On the other hand, the protein expression level of oat3 at leptomeninges was 6.65 fmol/µg protein, and the difference from choroid plexus was within two-fold. To investigate oat1's role, we injected para-aminohippuric acid (PAH) with or without oat1 inhibitors into cisterna magna (to minimize the contribution of choroid plexus function) of rats. A bulk flow marker, FITC-inulin, was not taken up from CSF up to 15 min, whereas uptake clearance of PAH was 26.5 µL/min. PAH uptake was completely blocked by 3 mM cephalothin (inhibits both oat1 and oat3), while 17% of PAH uptake was inhibited by 0.2 mM cephalothin (selectively inhibits oat3). These results indicate that oat1 and oat3 at the BAB provide a distinct clearance pathway of organic anion drugs from CSF independently of choroid plexus.

Can blockage or sacrifice of the middle meningeal artery lead to hydrocephalus?

BACKGROUND: The middle meningeal artery (MMA) is often sacrificed during neurosurgical procedures in the region of the pterion. This maneuver, herein, is hypothesized to be a potential reason for the development of postoperative hydrocephalus by injuring the vascular supply to the arachnoid granulations near the vertex of the skull, and thus disrupting their ability to allow for transfer of CSF from the subarachnoid space to the venous system. MATERIALS AND METHODS: To test this theory, the middle meningeal artery was isolated at the skull base and injected with India ink. Next, the superior sagittal sinus was opened and the arachnoid granulations inspected. RESULTS: All specimens demonstrated ink within the arachnoid granulations indicating that their blood supply is completely or at least partially via the middle meningeal artery. This finding with an illustrative case of surgical cautery of the middle meningeal artery at the skull base with subsequent development of hydrocephalus supports our hypothesis of potential role of iatrogenic MMA injury causing hydrocephalus. CONCLUSIONS: Our cadaveric study shows that the blood supply of the arachnoid granulations of the superior sagittal sinus is via the middle meningeal artery. Additional cases of postoperative hydrocephalus following middle meningeal artery sacrifice are needed to support our hypothesis.

Correlation between Hyperintense Vessels on FLAIR Imaging and Arterial Circulation Time on Cerebral Angiography.

PURPOSE: Hyperintense vessels (HVs) on fluid-attenuated inversion recovery (FLAIR) imaging are associated with the leptomeningeal collateral circulation in cases of arterial occlusive lesions. Nevertheless, the relationship between HVs on FLAIR imaging and arterial circulation time (ACT) on cerebral angiography has not been defined. METHODS: We analyzed images of 11 patients with acute occlusion of the distal internal carotid artery or proximal middle cerebral artery and calculated the difference in ACT (DACT) between infarcted and normal hemispheres. ACT was defined as the time interval from the initial opacification of the ipsilateral or contralateral cavernous internal carotid artery to the late arterial phase of the carotid artery territories. We scored HVs on FLAIR imaging using a modified Alberta Stroke Program Early Computerized Tomography Score (ASPECTS) and determined collateral circulation by grading collateral flow. RESULTS: We detected HVs on FLAIR images in 10 patients (median score, 4; range, 0 to 6). Comparison of infarcted and normal hemispheres demonstrated absent or subtle HVs on FLAIR imaging when the DACT was too short (7.98 s) and prominent HVs with moderate DACT (2 to 5 s). The score of HVs on FLAIR was estimated well by DACT using a quadratic regression model (R(2) = 0.602) and better than by grading collateral flow (R(2) = 0.256). CONCLUSION: In cases of large arterial occlusion, the hyperintensity of vessels on FLAIR images may be dependent on arterial circulation time via retrograde filling of the leptomeningeal collateral circulation.

Utilizing multiple scale models to improve predictions of extra-axial hemorrhage in the immature piglet.

Traumatic brain injury (TBI) is a leading cause of death and disability in the USA. To help understand and better predict TBI, researchers have developed complex finite element (FE) models of the head which incorporate many biological structures such as scalp, skull, meninges, brain (with gray/white matter differentiation), and vasculature. However, most models drastically simplify the membranes and substructures between the pia and arachnoid membranes. We hypothesize that substructures in the pia-arachnoid complex (PAC) contribute substantially to brain deformation following head rotation, and that when included in FE models accuracy of extra-axial hemorrhage prediction improves. To test these hypotheses, microscale FE models of the PAC were developed to span the variability of PAC substructure anatomy and regional density. The constitutive response of these models were then integrated into an existing macroscale FE model of the immature piglet brain to identify changes in cortical stress distribution and predictions of extra-axial hemorrhage (EAH). Incorporating regional variability of PAC substructures substantially altered the distribution of principal stress on the cortical surface of the brain compared to a uniform representation of the PAC. Simulations of 24 non-impact rapid head rotations in an immature piglet animal model resulted in improved accuracy of EAH prediction (to 94 % sensitivity, 100 % specificity), as well as a high accuracy in regional hemorrhage prediction (to 82-100 % sensitivity, 100 % specificity). We conclude that including a biofidelic PAC substructure variability in FE models of the head is essential for improved predictions of hemorrhage at the brain/skull interface.

Arachnoid membranes in the posterior half of the incisural space: an inverted Liliequist membrane-like arachnoid complex.

OBJECT: The aim of this study was to describe the similarity of configuration between the arachnoid complex in the posterior half of the incisural space and the Liliequist membrane. METHODS: Microsurgical dissection and anatomical observation were performed in 20 formalin-fixed adult cadaver heads. The origin, distribution, and configuration of the arachnoid membranes and their relationships with the vascular structures in the posterior half of the incisural space were examined. RESULTS: The posterior perimesencephalic membrane and the cerebellar precentral membrane have a common origin at the tentorial edge and form an arachnoid complex strikingly resembling an inverted Liliequist membrane. Asymmetry between sides is not uncommon. If the cerebellar precentral membrane is hypoplastic on one side or both, the well-developed quadrigeminal membrane plays a prominent part in partitioning the subarachnoid space in the posterior half of the incisural space. CONCLUSIONS: The arachnoid complex in the posterior half of the incisural space can be regarded as an inverted Liliequist membrane. This concept can help neurosurgeons to gain better understanding of the surgical anatomy at the level of the tentorial incisura.

Comparison of the global gene expression of choroid plexus and meninges and associated vasculature under control conditions and after pronounced hyperthermia or amphetamine toxicity.

BACKGROUND: The meninges (arachnoid and pial membranes) and associated vasculature (MAV) and choroid plexus are important in maintaining cerebrospinal fluid (CSF) generation and flow. MAV vasculature was previously observed to be adversely affected by environmentally-induced hyperthermia (EIH) and more so by a neurotoxic amphetamine (AMPH) exposure. Herein, microarray and RT-PCR analysis was used to compare the gene expression profiles between choroid plexus and MAV under control conditions and at 3 hours and 1 day after EIH or AMPH exposure. Since AMPH and EIH are so disruptive to vasculature, genes related to vasculature integrity and function were of interest. RESULTS: Our data shows that, under control conditions, many of the genes with relatively high expression in both the MAV and choroid plexus are also abundant in many epithelial tissues. These genes function in transport of water, ions, and solutes, and likely play a role in CSF regulation. Most genes that help form the blood-brain barrier (BBB) and tight junctions were also highly expressed in MAV but not in choroid plexus. In MAV, exposure to EIH and more so to AMPH decreased the expression of BBB-related genes such as Sox18, Ocln, and Cldn5, but they were much less affected in the choroid plexus. There was a correlation between the genes related to reactive oxidative stress and damage that were significantly altered in the MAV and choroid plexus after either EIH or AMPH. However, AMPH (at 3 hr) significantly affected about 5 times as many genes as EIH in the MAV, while in the choroid plexus EIH affected more genes than AMPH. Several unique genes that are not specifically related to vascular damage increased to a much greater extent after AMPH compared to EIH in the MAV (Lbp, Reg3a, Reg3b, Slc15a1, Sct and Fst) and choroid plexus (Bmp4, Dio2 and Lbp). CONCLUSIONS: Our study indicates that the disruption of choroid plexus function and damage produced by AMPH and EIH is significant, but the changes may not be as pronounced as they are in the MAV, particularly for AMPH. Expression profiles in the MAV and choroid plexus differed to some extent and differences were not restricted to vascular related genes.

Leptomeningeal collaterals are associated with modifiable metabolic risk factors.

OBJECTIVE: We sought to identify potentially modifiable determinants associated with variability in leptomeningeal collateral status in patients with acute ischemic stroke. METHODS: Data are from the Keimyung Stroke Registry. Consecutive patients with M1 segment middle cerebral artery ± intracranial internal carotid artery occlusions on baseline computed tomographic angiography (CTA) from May 2004 to July 2009 were included. Baseline and follow-up imaging was analyzed blinded to all clinical information. Two raters assessed leptomeningeal collaterals on baseline CTA by consensus, using a previously validated regional leptomeningeal score (rLMC). RESULTS: Baseline characteristics (N = 206) were: mean age = 66.9 ± 11.6 years, median baseline National Institutes of Health Stroke Scale = 14 (interquartile range [IQR] = 11-20), and median time from stroke symptom onset to CTA = 166 minutes (IQR = 96-262). Poor collateral status at baseline (rLMC score = 0-10) was seen in 73 of 206 patients (35.4%). On univariate analyses, patients with poor collateral status at baseline were older; were hypertensive; had higher white blood cell count, blood glucose, D-dimer, and serum uric acid levels; and were more likely to have metabolic syndrome. Multivariate modeling identified metabolic syndrome (odds ratio [OR] = 3.22, 95% confidence interval [CI] = 1.69-6.15, p < 0.001), hyperuricemia (per 1mg/dl serum uric acid; OR = 1.35, 95% CI = 1.12-1.62, p < 0.01), and older age (per 10 years; OR = 1.34, 95% CI = 1.02-1.77, p = 0.03) as independent predictors of poor leptomeningeal collateral status at baseline. INTERPRETATION: Metabolic syndrome, hyperuricemia, and age are associated with poor leptomeningeal collateral status in patients with acute ischemic stroke.

Modified three-dimensional brain model for study of the trans-sylvian approach.

The trans-sylvian approach is one of the most frequently employed neurosurgical procedures, but it is difficult for medical students to understand the approach stereoscopically. A three-dimensional model equipped with an arachnoid membrane and sylvian vein was developed which can be repeatedly used to simulate surgery for the education of medical students and residents in the trans-sylvian approach. The model was prepared using existing models of the skull bone, brain, and cerebral artery. Polyvinylidene chloride film, commonly used as plastic wrap for food, was adopted for the arachnoid membrane, and wetted water-insoluble tissue paper for the arachnoid trabeculae. The sylvian vein was prepared by ligating woolen yarn with cotton lace thread at several sites. Students and residents performed the trans-sylvian approach under a microscope, and answered a questionnaire survey. Using this model, simulation of division of the arachnoid membrane and arachnoid trabeculae, and dissection of the sylvian vein was possible. In the questionnaire, the subjects answered 8 questions concerning understanding of the stereoscopic anatomy of the sylvian fissure, usefulness of the simulation, and interest in neurosurgical operation using the following ratings: yes, very much; yes; somewhat; not very much; or not at all. All items rated as 'yes, very much' and 'yes' accounted for more than 70% of answers. This model was useful for medical students to learn the trans-sylvian approach. In addition, repeated practice is possible using cheap materials, which is advantageous for an educational model.

Multiple spinal dural arteriovenous fistulae and deterioration post lumbar puncture.

We report a 73-year-old man presenting with bilateral leg numbness and weakness. Three spinal dural arteriovenous fistulae (SDAVF) were found after clinical deterioration post lumbar puncture (LP). This patient highlights the difficulties in the diagnosis and management of SDAVF, and the risks of LP.

Microsurgical and endoscopic anatomy of Liliequist's membrane: a complex and variable structure of the basal cisterns.

OBJECTIVE: Descriptions of Liliequist's membrane, as reported in the literature, vary considerably. In our cadaveric study of Liliequist's membrane, we attempted to clarify and define its anatomic features and boundaries, as well as its relationship with surrounding neurovascular structures. We describe the embryology of this membrane as a remnant of the primary tentorium. The clinical significance of our findings is discussed with respect to third ventriculostomy and surgical approaches to basilar tip aneurysms, suprasellar arachnoid cysts, and perimesencephalic hemorrhage. METHODS: Thirteen formalin-fixed adult cadaveric heads were injected with colored silicone. After endoscopic exploration of Liliequist's membrane, a bilateral frontal craniotomy was performed, and the frontal lobes were removed to fully expose Liliequist's membrane. RESULTS: Liliequist's membrane is a complex and highly variable structure that is composed of either a single membrane or two leaves. The membrane was absent in two specimens without any clear demarcation between the interpeduncular, prepontine, and chiasmatic cisterns. CONCLUSION: Understanding the variable anatomy of Liliequist's membrane is important, particularly to improve current and forthcoming microsurgical and endoscopic neurosurgical procedures. It is important as a surgical landmark in various neurosurgical operations and in the physiopathology of several pathological processes (suprasellar arachnoid cysts and perimesencephalic hemorrhage).

An autopsy case of Fabry disease with neuropathological investigation of the pathogenesis of associated dementia.

The pathogenesis of dementia associated with Fabry disease was examined neuropathologically in an autopsy case. The patient was a 47-year-old computer programmer who developed renal failure at the age of 36, necessitating peritoneal dialysis, and thereafter suffered in succession episodic pulmonary congestion, bradyacusia, heart failure, and dementia, before dying of acute myocardial infarction. MRI of the brain demonstrated leuko-araiosis. The CNS parenchyma showed widespread segmental hydropic swelling of axons in the bilateral cerebral and cerebellar deep white matter in addition to neuronal ballooning due to glycolipid storage in a few restricted nuclei and multiple tiny lacunae. Hydropic axonal swelling was also sparsely distributed in the pyramidal tract, pedunculus cerebellaris superior and brachium colliculi inferioris, but wallerian degeneration of these tracts was absent. Additional features included angiopathy of the subarachnoidal arteries due to Fabry disease, such as medial thickening resulting from glycolipid deposition in smooth muscle cells (SMCs) and adventitial fibrosis with lymphocytic infiltration, together with widespread subtotal or total replacement of medial SMCs by fibrosis, associated with prominent intimal fibrous thickening and undulation of the internal elastic membrane of medium-sized (1000-100 microm diameter) arteries. The findings in this case suggest that axonopathic leukoencephalopathy due to multisegmental hydropic swelling of axons in the bilateral cerebral deep white matter is responsible for the dementia associated with Fabry disease, and may be caused by ischemia resulting from widespread narrowing and stiffening of medium-sized subarachnoidal arteries and progressive heart failure.

Granulocyte-macrophage colony-stimulating factor enhances leptomeningeal collateral growth induced by common carotid artery occlusion.

BACKGROUND AND PURPOSE: Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to accelerate collateral growth (arteriogenesis) at the circle of Willis in rat brain. However, the effect of GM-CSF on leptomeningeal collateral growth has not been established. We examined the effect of unilateral common carotid artery (CCA) occlusion and GM-CSF treatment on leptomeningeal collateral growth in mice. METHODS: Adult mice were subjected to unilateral CCA occlusion or sham surgery followed by an alternate-day regimen of GM-CSF (20 microg/kg) or saline injection. On day 7, latex perfusion was performed in 1 set of mice to visualize the leptomeningeal vessels, and the number of Mac-2(+) monocytes/macrophages on the dorsal surface of the brain was counted. In another set of mice, on day 7, permanent ipsilateral middle cerebral artery (MCA) occlusion was performed, and infarct volume was measured. RESULTS: Leptomeningeal collateral growth was observed after CCA occlusion, and that was enhanced by GM-CSF treatment. An increase in the number of Mac-2(+) cells on the surface of the brain occurred after CCA occlusion and was enhanced by GM-CSF treatment. Seven days after CCA occlusion, GM-CSF treatment decreased the infarct size attributable to subsequent MCA occlusion. CONCLUSIONS: After CCA occlusion, GM-CSF treatment enhanced leptomeningeal collateral growth and decreased the infarct size after MCA occlusion in mice.

Ectopia of meningeal fibroblasts and reactive gliosis in the cerebral cortex of the mouse model of muscle-eye-brain disease.

Congenital muscular dystrophies with brain malformations, such as muscle-eye-brain disease, exhibit neural ectopias caused by overmigration of neurons. Such overmigration is evident in protein O-mannose beta-1,2-N-acetylglucosaminyltransferase (POMGnT1) knockout mouse, a model of muscle-eye-brain disease, caused by breaches in the pial basement membrane. We hypothesize that breaches in pial basement membrane disrupt the neural-meningeal boundary, resulting in ectopia of meningeal fibroblasts in the cerebral cortex and reactive gliosis. To test this hypothesis, the cerebral cortices of developing and adult POMGnT1 knockout mice were analyzed by immunostaining with cell-specific markers and by electron microscopy. The upper half of the cerebral cortex in the knockout mouse contained increased numbers of fibroblasts closely associated with capillaries. During development of the cerebral cortex in the knockout mice, breaches in pial basement membrane allowed emigration of overmigrated neurons into the developing pia-arachnoid, scattering its mesenchymal cells throughout the diffuse cell zone and resulting in ectopia of mesenchyme-derived fibroblasts in the upper half of the cortex. Glial fibrillary acidic protein (GFAP) immunostaining revealed that the upper half of the cerebral cortex in the knockout also contained increased numbers of cells with morphologies typical of reactive astrocytes compared with the wild type. Moreover, most of the GFAP-positive reactive astrocytes were in close contact with ectopic fibroblasts, suggesting that they were induced by the fibroblasts. Collectively, the data support the hypothesis that the cerebral cortex of POMGnT1 knockout mice is characterized by migration defects leading to disruption of the pia-arachnoid, ectopia of fibroblasts in the cortex, and reactive gliosis.

Meningioma in the posterior fossa without dural attachment.

A 14-year-old boy presented with a very rare meningioma in the posterior cranial fossa without dural attachment. Magnetic resonance imaging revealed a 3-cm, well-circumscribed, heterogeneously enhanced, round mass without dural tail sign in the right side of the posterior fossa. Right vertebral angiography revealed very faint tumor staining supplied by the right posterior inferior cerebellar artery. Total removal of the tumor was performed. Intraoperatively, the mass exhibited no attachment to the dura mater, cerebellar parenchyma, or choroid plexus, but was firmly attached to the arachnoid tissue near the foramen of Luschka. Histological and immunohistochemical studies established the diagnosis of meningothelial meningioma (World Health Organization grade I).

Morphological aspects of the traumatic chronic subdural hematoma capsule: SEM studies.

The morphology of the outer and inner membranes of traumatic chronic subdural hematomas (CSDHs) surgically removed from eight patients was investigated by scanning electron microscopy (SEM). Hematomas were divided into three groups based on time that had passed from the initiation of trauma to surgery. Structure of the CSDHs showed gradual morphological changes of the developing hematoma capsule. They initially included angiogenic and aseptic inflammatory reactions followed by progressive involvement of fibroblasts-proliferating and producing collagen fibrils. Numerous capillaries suggesting formation of new blood vessels were observed mainly in young hematomas removed between 15 and 21 days after trauma. In "older" hematomas (40 days after trauma), more numerous capillaries and thin-walled sinusoids were accompanied by patent, larger diameter blood vessels. Within the fibrotic outer membrane of the "oldest" hematoma capsules (60 or more days after trauma), especially in the area over the hematoma cavity, blood vessels were frequently occluded by clots. The results suggest dynamic changes in cellular and vascular organization of traumatic CSDH capsules paralleling the progression in hematoma age.