Paul A. Felts

Inflammation induced by innate immunity in the central nervous system leads to primary astrocyte dysfunction followed by demyelination

Primary loss and dysfunction of astrocytes may trigger demyelination, as seen in neuromyelitis optica, an inflammatory disease of the central nervous system. In most patients affected by this disease, injury to astrocytes is initiated by the action of autoantibodies targeting aquaporin 4 (AQP-4), a water channel on astrocytes. We show here that damage of astrocytes and subsequent demyelination can also occur in the absence of autoantibody-mediated mechanisms. Following injection of lipopolysaccharide into the white matter initial microglia activation is followed by a functional disturbance of astrocytes, mainly reflected by retraction of astrocytic foot processes at the glia limitans and loss of AQP-4 and connexins, which are involved in the formation of gap junctions between astrocytes and oligodendrocytes. Demyelination and oligodendrocyte degeneration in this model follows astrocyte pathology. Similar structural abnormalities were also seen in a subset of active lesions in multiple sclerosis. Our studies suggest that astrocyte injury may be an important early step in the cascade of lesion formation in brain inflammation.

Internodal potassium currents can generate ectopic impulses in mammalian myelinated axons

Positive clinical symptoms can arise from ectopic action potentials in several disorders of myelinated axons. Here we report that an elevated K+ concentration in the periaxonal, internodal space can cause internodal K+ currents to become excitatory, resulting in slow potential oscillations and associated bursts of ectopic spikes. Ectopic firing may therefore be favoured by conditions in which periaxonal K+ buffering is compromised.

The feasibility of micro‐ultrasound as a tool to image peripheral nerves

Despite widespread use of ultrasound imaging to guide needle placement, the incidence of transient and permanent nerve damage as a complication of regional anaesthesia has not changed over the last decade. In view of the controversy surrounding intraneural injection there is a need to understand the structural changes caused by subepineural and subperineural needle penetration. Clinical ultrasound machines do not provide adequate anatomical resolution, and anaesthetists have difficulty judging the precise location of the needle tip relative to the epineurium. We studied the suitability of micro‐ultrasound imaging (which offers anatomical resolution better than 100 μm) as a tool for viewing neural anatomy and deformation caused by needle insertion. The primary objective was to assess micro‐ultrasound imaging as a method to view fascicles within nerves resected from fresh and soft‐embalmed cadavers. Secondary objectives were to observe any disruption of the neural anatomy caused by anaesthetic needle penetration, and to assess the integrity of fresh and Thiel method soft‐embalmed nerves, after handling and during needle insertion using ultrasound images and histology. We imaged nine nerves from the left and right sides of fresh and soft‐embalmed cadavers. A regional block needle was inserted into three median nerves. We identified fascicles > 0.4 mm in width using micro‐ultrasound. Subepineural needle placement was associated with denting, rotation and elastic deformation of fascicles, whereas subperineural needle insertion split fascicles permanently.

Neuregulins in Schwann Cell Development

In the PNS, Schwann cells are important both as support cells for small, unmyelinated axons, and for support and the production of myelin sheaths around larger axons, thereby permitting rapid axonal conduction. During development, successful myelination requires that Schwann cell precursors develop from multipotential cells within the neural crest, avoid apoptotic cell death, migrate with developing nerves, proliferate, and, finally, mature into myelinating Schwann cells. Recently, the important role of a large family of growth factors, termed the neuregulins (NRGs), in this developmental progression has begun to be elucidated. NRGs are produced by several cell types, including developing sensory and motor neurons, whose axons will project to the peripheral nerves. In NRG knockout animals, there is a severe reduction in the number of Schwann cell precursors in neural crest-derived peripheral ganglia, which indicates that NRGs are important beginning early in Schwann cell development. Presented here is a brief update of recent progress in our understanding of the actions of NRGs in Schwann cell development, and of the inter actions between NRGs and their receptors. NEUROSCIENTIST 5:8-11, 1999

Histology, vascularity and innervation of the glenoid labrum:

Background: Although the glenoid labrum has an important role in shoulder stability, little is known about its composition, vascularity and innervation. The aims of this study were therefore to evaluate the histology, vascularity and innervation of the glenoid labrum. Materials and methods: Ten glenoid labrum specimens (three male, two female: mean age 81.2 years, range 76–90 years) were detached at the glenoid neck. Following decalcification, sections were cut through the whole thickness of each specimen perpendicular to the glenoid labrum at 12 radii corresponding to a clock face superimposed on the glenoid fossa. Then they were stained using haematoxylin and eosin, a silver nitrate protocol or subjected to immunohistochemistry using anti-protein gene protein 9.5 to demonstrate neuronal processes. Results: The labrum was fibrocartilaginous, being more fibrous in its free margin. There was a variable distribution of blood vessels, being more vascular in its periphery, with many originating from the fibrous capsule and piercing the glenoid labrum. Immunohistochemistry revealed positive staining of nerve fibres within the glenoid labrum. Conclusion: The glenoid labrum is fibrocartilaginous, being more fibrous in its periphery, and is vascularized, with the anterosuperior aspect having a rich blood supply. Free sensory nerve fibres were also present; no encapsulated mechanoreceptors were observed. The presence of sensory nerve fibres in the glenoid labrum could explain why tears induce pain. It is postulated that these sensory fibres could play a role in glenohumeral joint proprioception.

Blood supply and vascularity of the glenoid labrum: Its clinical implications:

Background: Tears of the glenoid labrum are common after dislocation of the glenohumeral joint. The outcome for healing or surgical reconstruction of the glenoid labrum relies on the extent of its vascularization. This study aims to evaluate the glenoid labrum blood supply and to determine its regional vascularity. Materials and Methods: A total of 140 shoulders (30 male and 40 female cadavers) were examined: mean age 81.5 years, range 53–101 years. All blood vessels around the glenohumeral joint were dissected and recorded. Ten specimens with the glenoid labrum and fibrous capsule attached were randomly selected and detached at the glenoid neck and subjected to decalcification. Sections (10–20 μm) were cut through the whole thickness of each specimen from the centre of the glenoid fossa perpendicular to the glenoid labrum at 12 radii corresponding to a clock face superimposed on the glenoid. Sections were stained using haematoxylin and eosin and then examined. Results: The blood supply to the glenoid labrum is by direct branches from the second part of the axillary artery, subscapular, circumflex scapular and anterior circumflex humeral and posterior circumflex humeral arteries, as well as branches of muscular arteries supplying the surrounding muscles. Conclusion: This study shows that the glenoid labrum has a rich blood supply suggesting that, regardless of the types of the glenoid labrum lesions or their management, an excellent outcome for glenoid labrum healing and joint stability is possible. The observations also suggest that the blood supply to the glenoid labrum is sufficient, enabling its reattachment.

Quantification of Osteon Morphology Using Geometric Histomorphometrics.

Many histological methods in forensic anthropology utilize combinations of traditional histomorphometric parameters which may not accurately describe the morphology of microstructural features. Here, we report the novel application of a geometric morphometric method suitable when considering structures without anatomically homologous landmarks for the quantification of complete secondary osteon size and morphology. The method is tested for its suitability in the measurement of intact secondary osteons using osteons digitized from transverse femoral diaphyseal sections prepared from two human individuals. The results of methodological testing demonstrate the efficacy of the technique when applied to intact secondary osteons. In providing accurate characterization of micromorphology within the robust mathematical framework of geometric morphometrics, this method may surpass traditional histomorphometric variables currently employed in forensic research and practice. A preliminary study of the intersectional histomorphometric variation within the femoral diaphysis is made using this geometric histomorphometric method to demonstrate its potential.

Demyelination Models in the Spinal Cord

Disruption of axonal conduction within the central nervous system has obvious, negative consequences on numerous functions, including the ability to execute movement successfully. One important cause of axonal conduction deficits is primary demyelination, that is, the loss of the myelin sheaths but sparing of the axons which they surround. Such demyelination leads to conduction deficits ranging from action potential slowing and loss of transmission fidelity, to conduction block, and this latter, most severe consequence is almost inevitably the first consequence of the loss of a whole internode(s) of myelin. Several methods have been developed to induce primary demyelination in the spinal cord and some of the more common of these will be discussed in this chapter.