Gabor Baksa

Neurochemical mapping of the human hippocampus reveals perisynaptic matrix around functional synapses in Alzheimer’s disease

Perineuronal matrix is an extracellular protein scaffold to shape neuronal responsiveness and survival. Whilst perineuronal nets engulf the somatodendritic axis of neurons, axonal coats are focal extracellular protein aggregates surrounding individual synapses. Here, we addressed the chemical identity and subcellular localization of both perineuronal and perisynaptic matrices in the human hippocampus, whose neuronal circuitry is progressively compromised in Alzheimer’s disease. We hypothesized that (1) the cellular expression sites of chondroitin sulphate proteoglycan-containing extracellular matrix associate with specific neuronal identities, reflecting network dynamics, and (2) the regional distribution and molecular composition of axonal coats must withstand Alzheimer’s disease-related modifications to protect functional synapses. We show by epitope-specific antibodies that the perineuronal protomap of the human hippocampus is distinct from other mammals since pyramidal cells but not calretinin+ and calbindin+ interneurons, neurochemically classified as novel neuronal subtypes, lack perineuronal nets. We find that cartilage link protein-1 and brevican-containing matrices form isolated perisynaptic coats, engulfing both inhibitory and excitatory terminals in the dentate gyrus and entorhinal cortex. Ultrastructural analysis revealed that presynaptic neurons contribute components of perisynaptic coats via axonal transport. We demonstrate, by combining biochemical profiling and neuroanatomy in Alzheimer’s patients and transgenic (APdE9) mice, the preserved turnover and distribution of axonal coats around functional synapses along dendrite segments containing hyperphosphorylated tau and in amyloid-β-laden hippocampal microdomains. We conclude that the presynapse-driven formation of axonal coats is a candidate mechanism to maintain synapse integrity under neurodegenerative conditions.

Perisynaptic aggrecan-based extracellular matrix coats in the human lateral geniculate body devoid of perineuronal nets

The extracellular matrix surrounds different neuronal compartments in the mature nervous system. In a variety of vertebrates, most brain regions are loaded with a distinct type of extracellular matrix around the somatodendritic part of neurons, termed perineuronal nets. The present study reports that chondrotin sulfate proteoglycan‐based matrix is structured differently in the human lateral geniculate body. Using various chondrotin sulfate proteoglycan‐based extracellular matrix antibodies, we show that perisomatic matrix labeling is rather weak or absent, whereas dendrites are contacted by axonal coats appearing as small, oval structures. Confocal laser scanning microscopy and electron microscopy demonstrated that these typical structures are associated with synaptic loci on dendrites. Using multiple labelings, we show that different chondrotin sulfate proteoglycan components of the extracellular matrix do not associate exclusively with neuronal structures but possibly associate with glial structures as well. Finally, we confirm and extend previous findings in primates that intensity differences of various extracellular matrix markers between magno‐ and parvocellular layers reflect functional segregation between these layers in the human lateral geniculate body.

Intraosseous territory of the facial artery in the maxilla and anterior mandible: Implications for allotransplantation

AIM The aim of this anatomical study was to define the intraosseous vascular territory of the facial artery. The clinical issue is whether ipsilateral facial artery anastomosis will guarantee blood supply to the ipsi- and contralateral mandibular symphyses and maxillae in allotransplantation. MATERIAL AND METHODS Of 10 human cadaveric heads, the left facial artery was injected with a positive contrast agent. The maxillae and mandibular symphyses were investigated with cone-beam computed tomography (CBCT). RESULTS Each ipsilateral maxilla and mandibular bone segment showed contrast medium in the intraosseous vessels. In 50% of cases, this was also the case on the contralateral side of the maxilla and anterior mandible. CONCLUSIONS The maxillae and the mandibular symphyses receive ipsilateral blood supply from the facial artery and, in 50% of cases, also from the contralateral facial artery. Internal maxillary artery anastomosis is not required for a vascularized maxillary bone flap. Additionally, involvement of the submental artery is not needed for a mandibular symphyseal bone flap.

Endoscopic anatomical study of the arachnoid architecture on the base of the skull. Part I: The anterior and middle cranial fossa

Abstract Minimally invasive neurosurgery requires a detailed knowledge of microstructures, such as the arachnoid membranes. In spite of many articles addressing arachnoid membranes, its detailed organization is still not well described. The aim of this study is to investigate the topography of the arachnoid in the anterior cranial fossa and the middle cranial fossa. Rigid endoscopes were introduced through defined keyhole craniotomies, to explore the arachnoid structures in 110 fresh human cadavers. We describe the topography and relationship to neurovascular structures and suggest an intuitive terminology of the arachnoid. We demonstrate an “arachnoid membrane system”, which consists of the outer arachnoid and 23 inner arachnoid membranes in the anterior fossa and the middle fossa. The inner membranes are arranged in two “arachnoid membrane groups” in the examined regions. The first is the carotid membrane group, located in the suprasellar region, consisting of seven paired and three unpaired inner membranes and the outer arachnoid on its base. The second is the Sylvian membrane group, composed of three inner membranes of the Sylvian fissure and completed by the outer arachnoid. Our findings should be very helpful in understanding the complex organization of the cranial arachnoid, which is mandatory for the safe and effective use of minimally invasive endoscopic techniques.

Endoscopic approach-routes in the posterior fossa cisterns through the retrosigmoid keyhole craniotomy: an anatomical study

Endoscopy in cerebellopontine angle surgery is an increasingly used technique. Despite of its advantages, the shortcomings arising from the complex anatomy of the posterior fossa are still preventing its widespread use. To overcome these drawbacks, the goal of this study was to define the anatomy of different endoscopic approaches through the retrosigmoid craniotomy and their limitations by surgical windows. Anatomical dissections were performed on 25 fresh human cadavers to describe the main approach-routes. Surgical windows are spaces surrounded by neurovascular structures acting as a natural frame and providing access to deeper structures. The approach-routes are trajectories starting at the craniotomy and pointing to the lesion, passing through certain windows. Twelve different windows could be identified along four endoscopic approach-routes. The superior route provides access to the structures of the upper pons, lower mesencephalon, and the upper neurovascular complex through the suprameatal, superior cerebellar, and infratrigeminal windows. The supratentorial route leads to the basilar tip and some of the suprasellar structures via the ipsi- and contralateral oculomotor and dorsum sellae windows. The central endoscopic route provides access to the middle pons and the middle neurovascular complex through the inframeatal, AICA, and basilar windows. The inferior endoscopic route is the pathway to the medulla oblongata and the lower neurovascular complex through the accessory, hypoglossal, and foramen magnum windows. The anatomy and limitations of each surgical windows were described in detail. These informations are essential for safe application of endoscopy in posterior fossa surgery through the retrosigmoid approach.

Applied anatomy of a minimally invasive muscle-splitting approach to posterior C1-C2 fusion: an anatomical feasibility study.

AbstractPurpose To describe the applied anatomy of a minimally invasive muscle-splitting approach used to reach the posterior aspect of the C1–C2 complex.Summary of background dataAtlantoaxial fusion using a midline posterior approach and polyaxial screw and rod system is widely used. Although minimally invasive variations of this technique have been recently reported, the complex applied anatomy of these approaches has not been described. The C1–C2 complex represents an unique challenge because of its bony and vascular anatomy. In this study, the applied anatomy and feasibility of this technique are examined on cadavers.MethodsThe microsurgical anatomy of the upper cervical spine is examined on a formalin-fixed and on a fresh cadaver. The muscle-splitting approach is performed on 12 fresh cadavers using this technique.ResultsThe minimally invasive muscle-splitting approach is described in detail. Relevant anatomy and bony landmarks that aid screw placement in C1 and C2 could be well visualized. Using this approach, we were able to reach the lateral mass of the atlas and the inferior articular process and pars interarticularis of the axis in all of the nine cadavers. We placed mini polyaxial screws in C1 lateral mass and C2 pars interarticularis in four cadavers according to the technique described by Harms and Melcher.Conclusions Using this approach, it was possible to reach the posterior aspect of C1 and C2; the relevant anatomy needed to perform a C1–C2 fusion could be well visualized.

TNAP activity is localized at critical sites of retinal neurotransmission across various vertebrate species.

Evidence is emerging with regard to the role of tissue non-specific alkaline phosphatase (TNAP) in neural functions. As an ectophosphatase, this enzyme might influence neural activity and synaptic transmission in diverse ways. The localization of the enzyme in known neural circuits, such as the retina, might significantly advance an understanding of its role in normal and pathological functioning. However, the presence of TNAP in the retina is scarcely investigated. Our multispecies comparative study (zebrafish, cichlid, frog, chicken, mouse, rat, golden hamster, guinea pig, rabbit, sheep, cat, dog, ferret, squirrel monkey, human) using enzyme histochemistry and Western blots has shown the presence of TNAP activity in the retina of several mammalian species, including humans. Although the TNAP activity pattern varies across species, we have observed the following trends: (1) in all investigated species (except golden hamster), retinal vessels display TNAP activity; (2) TNAP activity consistently occurs in the photoreceptor layer; (3) in majority of the investigated species, marked TNAP activity is present in the outer and inner plexiform layers. In zebrafish, frog, chicken, guinea pig, and rat, TNAP histochemistry has revealed several sublayers of the inner plexiform layer. Frog, golden hamster, guinea pig, mouse, and human retinas possess a subpopulation of amacrine cells positively staining for TNAP activity. The expression of TNAP in critical sites of retinal signal transmission across a wide range of species suggests its fundamental, evolutionally conserved role in vision.

Region Specific Differences of Claudin-5 Expression in Pediatric Intracranial Ependymomas: Potential Prognostic Role in Supratentorial Cases

Ependymomas are common pediatric brain tumors that originate from the ependyma and characterized by poor prognosis due to frequent recurrence. However, the current WHO grading system fails to accurately predict outcome. In a retrospective study, we analyzed 54 intracranial pediatric ependymomas and found a significantly higher overall survival in supratentorial cases when compared to infratentorial tumors. Next we performed region-specific immunohistochemical analysis of the ependyma in neonatal and adult ependyma from the central canal of spinal cord to the choroid plexus of lateral ventricles for components of cell-cell junctions including cadherins, claudins and occludin. We found robust claudin-5 expression in the choroid plexus epithelia but not in other compartments of the ependyma. Ultrastructural studies demonstrated distinct regional differences in cell-cell junction organization. Surprisingly, we found that 9 out of 20 supratentorial but not infratentorial ependymomas expressed high levels of the brain endothelial tight junction component claudin-5 in tumor cells. Importantly, we observed an increased overall survival in claudin-5 expressing supratentorial ependymoma. Our data indicates that claudin-5 expressing ependymomas may follow a distinct course of disease. The assessment of claudin-5 expression in ependymoma has the potential to become a useful prognostic marker in this pediatric malignancy.

Endoscopic anatomy of the intracisternal oculomotor nerve: a new segmentation based on the topography of the arachnoid membranes

Abstract Objective: The aim of our study was to investigate the detailed endoscopic anatomy of the intracisternal portion of the oculomotor nerve and to update the present knowledge of its related anatomy with the newest research on the topography of the arachnoid membrane system of the skull base. Methods: This study was performed on 50 fresh human cadaveric specimens post-mortem not more than 72 h. In each specimen, the intracranial arterial system was injected with red gelatin solution. We used the endoscope-controlled and endoscope-assisted microsurgical techniques applied through the minimally invasive supraorbital keyhole craniotomy to perform our dissections. Results: We divided the intracisternal oculomotor nerve into three segments in this study. These are the interpeduncular segment, located in the interpeduncular fossa and surrounded by dens arachnoid trabeculae around the thalamoperforating arteries; the tentorial segment, located between the posterior cerebral and superior cerebellar arteries and the posterior petroclinoid fold and surrounded by the elements of the clival and tentorial arachnoid membrane groups; and the trigonal segment located on the surface of the oculomotor trigone between the posterior petroclinoid fold and the dural exit of the nerve into the cavernous sinus and surrounded by the posteriorly located membranes of the carotid membrane group. Conclusions: Our findings support the more accurate understanding of the physiology of the arachnoid membrane system and the pathophysiology of space-occupying lesions in the region of the oculomotor nerve. Therefore, our results may support performing more atraumatic surgery in this area.

Primary Obstruction of the Foramen of Luschka: Anatomy, Histology, and Clinical Significance

BACKGROUND The foramen of Luschka is a natural aperture between the fourth ventricle and the subarachnoid space at the cerebellopontine angle. Membranous closure of this foramen is referred to as primary obstruction. Available information about this variant and its role in the development of the cysts of the posterior fossa is contradictory. METHODS The macroscopic and histologic features of the obstructed foramina were examined in 61 formalin-fixed human brains (122 foramina). Three rhomboid lips of various sizes with lateral recess were used for comparison. Five postoperative cases of diverticulum of the foramen of Luschka were included in this study, with 1 case presented in detail to illustrate anatomic and histologic findings. RESULTS Primary obstruction was present in 11 of 122 cases. In 1 case, an enlarged rigid pouch with a thick wall was found. The wall of the membrane in primary obstruction and the rhomboid lip were composed of an inner ependymal, a middle glial, and an outer leptomeningeal layer. CONCLUSIONS The rhomboid lip is a remnant of the roof of the fourth ventricle. Imperforation of the foramen of Luschka results in a pouch in the cerebellopontine angle that contains choroid plexus (Bochdaleks flower basket) and communicates with the fourth ventricle. This pouch has the potential to grow to a diverticulum and cause clinical symptoms. Based on our clinical observations, detailed radiologic and surgical-anatomic criteria were proposed to support the differential diagnosis of a diverticulum of the foramen of Luschka. Treatment strategies were also suggested.