The purpose of this study was to test the effectiveness of implants derived from peripheral neural tissue to serve as bridges following interruption of the developing corticospinal tract (CST). Implants prepared from purified populations of cultured dorsal root ganglion neurons (DRGNs) and Schwann cells (SCs) (Kuhlengel et al., J. Comp. Neurol. 293:63-73, 1990) were placed into thoracolumbar regions of neonatal rat spinal cord from which a 2-mm length of dorsal columns had been removed by suction. These cords were examined by a number of techniques 10 days to 6 months later. The implants, recognizable by their DRGN content, filled the vacated dorsal columns and survived the longest periods examined. The most effective method to maintain implant position was dorsal placement of collagen-coated Nitex filter. Implants were inserted either at the time of lesioning or 5 days later. The implant survival rate was better (72% vs. 50%) and meningeal scarring was less with immediate implantation, but delayed implantation resulted in better implant-cord fusion and the implant better filled the lesion cavity. DRGN/SC implants became well vascularized without leptomeningeal cells; this may explain why implant survival was not improved with leptomeningeal cell addition. Particularly well-differentiated implants (full extracellular matrix production and myelination) did not fuse as well with cord as did those less well differentiated. The addition of nerve growth factor to the Nitex filter collagen coating led to improved survival of DRGNs in implants. Electron microscopy showed that astrocytes populated the implant-cord junction region and migrated into implants. Typical SCs related to nonmyelinated and myelinated axons were present in implants. Close proximity of astrocytes and central myelin to SCs and peripheral myelin demonstrated good implant integration with cord. Clusters of SCs, astrocytes, and axons, all enclosed within a common basal lamina, were observed in implants. Immunostaining for GFAP and laminin confirmed our microscopy findings that SCs did not migrate from implant into host but that astrocytes left host tissue to enter implants. Neuroanatomical tracing of CST neurons with HRP-WGA showed that labeled fibers were not present in the implant but were fasciculated just beneath in gray matter. These fibers remained clustered in gray matter underneath the ventral dorsal columns caudal to the lesion. In lesioned but not implanted rats, labeled fibers were only diffusely distributed in gray matter. Delayed implantation led to more variation in fasciculation compared with immediate implantation.(ABSTRACT TRUNCATED AT 400 WORDS)
Our goal was to devise methods of implanting defined populations of the cellular constituents of peripheral nerve into regions of spinal cord injury. This objective derived from the knowledge that the cellular environment of peripheral nerve is known to be supportive of axon regeneration from both central and peripheral neurons. Two of the constituents of the peripheral nerve environment known to influence axonal growth are the Schwann cell and extracellular matrix (particularly basal lamina), both of which can be obtained in culture. We describe here large-scale methods of establishing purified populations of rat sensory neurons to which purified populations of Schwann cells were added. These essentially monolayer preparations were then scrolled and cut into lengths of proper shape and size to provide implants for sites of spinal cord injury in newborn rats. We also describe methods enabling the addition of leptomeningeal components to the implants; this addition contributes a proliferating population of vascular endothelial cells (identified by immunostaining) to the otherwise vasculature-free neuron/Schwann cell implant. Light and electron microscopic observations were made to characterize the implants. When the implant was ready for use, it contained Schwann cells that were differentiated, i.e., had begun to ensheathe axons and form basal lamina. The use of a medium containing human plasma to foster endothelial cell growth led to increased neurite fasciculation and Schwann cell migratory activity in the outgrowth, particularly when the neurons and Schwann cells were cultured on leptomeninges. The second paper in this series reports the deportment of these implants and their influence on corticospinal tract growth after placement into regions of dorsal column injury in neonatal rats (Kuhlengel et al., J. Comp. Neurol 293:74-91, 1990).
Spontaneous spinal epidural haematoma is an unusual but well recognized cause of compressive myelopathy or cauda equina syndrome. Radicular pain is one of the earliest symptoms and a hallmark of spontaneous spinal epidural haematoma, as in the case of cervical spondylosis and disc prolapse. Should an epidural haematoma be located in the cervical spine, the resultant cervical radicular pain may sometimes be erroneously attributed to a cardiac cause, especially in the setting of pre-existing cardiac disease. The error in diagnosis can lead to another pitfall, the addition of heparin. If the etiology of the pain is a cervical epidural haematoma this can have grave consequences. Moreover, patients with cardiac ischemia who are treated with anticoagulants may rarely develop a cervical epidural haematoma. The resulting radicular pain can overlap with cardiac pain and escape recognition. Symptoms of neck and upper extremity pain with bilateral signs of myelopathy with a sensory level should lead to a suspicion of acute cervical cord compression. The addition of heparin can only compound the disastrous consequence of a rapidly expanding spinal epidural haematoma. The following cases illustrate this diagnostic and therapeutic conundrum.
The halo cervical orthosis has proven extremely effective in stabilizing the spine, both non-operatively and as a supplement to operative procedures. Current designs of the available halo utilize either a closed or an open stabilizing ring. Twenty-four patients with various indications for halo application are reviewed. Eleven were treated with a closed ring apparatus (Ace Medical, Los Angeles, California), and thirteen with an open ring device (Bremer, Inc, Jacksonville, Florida). X-rays of the treated patients were compared by group, and patients were interviewed regarding their complaints while wearing the halo. Rates of complication were compared. Results showed no significant differences between radiographs (kyphosis or translation) throughout the follow-up period. Patients experienced a significantly higher incidence of halo-associated pain in the open group. Otherwise, there were no statistical differences in the complication rates of either device. Whether or not the higher incidence of pain in the open group is related to decreased device rigidity is unknown. The open design may theoretically permit bending and opening of the ring to occur, the so-called 'wishbone' effect. Based on these data, it cannot be determined whether the advantages of the open ring-ease of application-are offset by this potential disadvantage. Clearly, a larger, randomized prospective study is required to investigate this.
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