The effects of tubulation on healing and scar formation after transection of the adult rat spinal cord.

PURPOSE: The purpose of this study was to characterize the effects of implantation of a collagen tube on healing and scar formation following transection of tbc adult rat spinal cord. METHODS: The spinal cords of adult rats were completely transected at the mid-thoracic level. At 30 days after injury, the cellular and extra-cellular components of repair tissue present within tubulated and non-tubulated (control) wounds were compared using qualitative and quantitative histological techniques. RESULTS: The presence of the tube reduced fibrocollagenous scar invasion into the gap, promoted astrocyte migration, and oriented axonal and connective tissue components of the repair tissue. Tube implants supported the regeneration of a substantial number of myelinated axons. A notable finding was the identification of cells containing a contractile actin isoform in the healing spinal cord. CONCLUSIONS: The tubulation model allows for the study of spinal cord wound healing and axon elongation in a controlled experimental environment within the tube lumen. Using this model, it will be possible to study manipulation of the healing response by the introduction of exogenous agents within the tube.

Early peripheral nerve healing in collagen and silicone tube implants: myofibroblasts and the cellular response.

Injuries to peripheral nerves innervating a limb cause paralysis, and can necessitate amputation. The inability of the nerves to regenerate spontaneously and the limitations of autograft procedures led to the development of treatments involving insertion of the nerve ends into prosthetic tubular devices. Previous work showed that 'entubulation' of the nerve ends in a silicone tube containing a specific porous, resorbable collagen-GAG (CG) copolymer, serving as an analog of extracellular matrix, improved regeneration compared to an empty silicone tube. However, long-term treatment with silicone tubes produced constriction that caused partial degradation of the regenerated axons; for this and other reasons, implementation of a nondegradable tube may require a second surgical procedure for removal. In this study the silicone tube was replaced with porous and non-porous collagen tubes in order to produce fully degradable devices. CG-filled collagen tubes and controls (CG-filled silicone tubes and empty collagen and silicone tubes) were implanted in a 10-mm gap in the rat sciatic nerve, with three rats in each group. The regeneration was evaluated after six weeks using light microscope images of cross sections of the nerve that were digitized and analyzed. Histograms of the diameters of the axons were generated and compared. The cellular response to the implanted biomaterials was assessed histologically, and immunohistochemistry was performed using an antibody to alpha-smooth muscle actin in order to determine the presence of myofibroblasts (contractile cells). Axonal regrowth was comparable in porous collagen, non-porous collagen, and silicone tubes filled with a CG matrix. These results support the implementation of a degradable collagen tube in place of a silicone device. Confirming earlier work, regeneration through the silicone and collagen tubes was enhanced by the CG copolymer, compared to empty tubes. A notable finding was a continuous layer of myofibroblasts on the surfaces of all of the six silicone tube prostheses, but on the inner surface of only one of six collagen tubes (Fisher's exact tests; P < 0.01). This is the first report of contractile capsules around silicone tubes, and supports the use of degradable collagen tubes in peripheral nerve regeneration. Macrophages were found bordering both the silicone and collagen tubes, and in the case of the collagen tubes, appeared to be participating in the regulation of the tubes.

High-frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor.

Pharmacologic treatment for essential tremor and the tremor of Parkinson's disease is often inadequate. Stereotaxic surgery, such as thalamotomy, can effectively reduce tremors. We performed a multicenter trial of unilateral high-frequency stimulation of the ventral intermedius nucleus of the thalamus in 29 patients with essential tremor and 24 patients with Parkinson's disease, using a blinded assessment at 3 months after surgery to compare clinical rating of tremor with stimulation ON with stimulation OFF and baseline and a 1-year follow-up. Six patients were not implanted because of lack of intraoperative tremor suppression (2 patients), hemorrhage (2 patients), withdrawal of consent (1 patient), and persistent microthalamotomy effect (1 patient). A significant reduction in both essential and parkinsonian tremor occurred contralaterally with stimulation. Patients reported a significant reduction in disability. Measures of function were significantly improved in patients with essential tremor. Complications related to surgery in implanted patients were few. Stimulation was commonly associated with transient paresthesias. Other adverse effects were mild and well tolerated. Efficacy was not reduced at 1 year. Chronic high-frequency stimulation is safe and highly effective in ameliorating essential and parkinsonian tremor.

An embryonic origin for medulloblastoma.

Medulloblastoma is a common brain tumor of children. Three differentiated cell types are found in medulloblastomas: neurons, glia, and muscle cells. Because of the presence of multiple differentiated cell types these tumors were named after a postulated cerebellar stem cell, the medulloblast, that would give rise to the differentiated cells found in the tumors. We describe a cell line with the properties expected of the postulated medulloblast. The rat cerebellar cell line ST15A expresses an intermediate filament, nestin, that is characteristic of neuroepithelial stem cells. ST15A cells can differentiate, gaining either neuronal or glial properties. In this paper we show that the same clonal cell can also differentiate into muscle cells. This result suggests that a single neuroectodermal cell can give rise to the different cell types found in medulloblastoma. We also show expression of nestin in human medulloblastoma tissue and in a medulloblastoma-derived cell line. Both the properties of the ST15A cell line and the expression of nestin in medulloblastoma support a neuroectodermal stem cell origin for this childhood tumor.

Meningeal metastasis of leiomyosarcoma mimicking meningioma: CT and MR findings.

A case of leiomyosarcoma metastatic to the meninges is reported. The tumor had imaging features typical for meningioma on CT and postcontrast magnetic resonance.

Some cholecystokinin-8 immunoreactive fibers in large pial arteries originate from trigeminal ganglion.

Cholecystokinin-8 immunoreactive (CCK8I) nerve fibers were demonstrated in whole mount preparations and cross-sections of pial blood vessels in the cat, guinea pig and rat using a specific antiserum and the avidin-biotin-peroxidase complex method. Positive fibers were present in nearly all pial arteries examined, and were located in the adventitial layer and at the junction of the adventitia and media. In general, CCK8I fibers were less abundant than substance P immunoreactive (SPI) fibers visualized in the same vessels. A marked depletion of CCK8I was noted in large cerebral arteries following treatment of adult guinea pigs with capsaicin, a drug shown previously to deplete CCK8 in some primary sensory neurons. The density of CCK8I-containing fibers was also decreased in the ipsilateral vessels of the cat circle of Willis following unilateral trigeminal ganglionectomies. These results indicate that CCK8I is contained in afferent fibers within large pial arteries of Willis' circle which project from neurons in the ipsilateral trigeminal ganglion. Whether CCK8 coexists with SP in these fibers remains to be determined.

Trigeminal afferents to cerebral arteries and forehead are not divergent axon collaterals in cat.

Horseradish peroxidase conjugated to wheat germ agglutinin (HRP-WGA), and bisbenzimide (a fluorescent dye) were used as retrograde axonal tracers to examine whether or not intracranial and extracranial trigeminal afferents represent divergent axon collaterals. HRP-WGA was applied to the proximal segment of the middle cerebral artery and bisbenzimide was injected into a branch of the ophthalmic nerve in 5 cats. Histologic examination of the ipsilateral trigeminal ganglion revealed HRP-labeled cell bodies located among clusters of cells exhibiting bisbenzimide fluorescence. Cells containing both labels were not observed. These results support the concept that divergent axon collaterals are probably not involved in the pathogenesis of referred pain during vascular headache.

Substance P and the sensory innervation of intracranial and extracranial feline cephalic arteries. Implications for vascular pain mechanisms in man.

Substance P, a putative neurotransmitter peptide present in a subpopulation of small sensory neurons, was measured in the walls of feline cranial arteries and systemic veins and arteries using a sensitive and specific radioimmunoassay. Substance P immunoreactivity exhibited a retention time identical to that of synthetic substance P when vessel extracts were subjected to reverse phase high performance liquid chromatography. Levels in cephalic arteries (453-1083 fmol/mg protein) were at least twice as high as amounts in systemic arteries and veins, and were significantly higher than those measured in the cornea and lip. Unilateral excision of the trigeminal ganglion decreased the peptide by 44 to 86 per cent in ipsilateral intracranial and extracranial arteries (e.g. external and internal maxillary, lingual, temporal, anterior, middle and posterior cerebral, superior cerebellar and posterior communicating arteries). Extracranial arteries were decreased on average by 78 per cent, whereas intracranial arteries were reduced by 55 per cent. Unilateral removal of the superior cervical sympathetic ganglion was without effect. The described pattern of sensory innervation provides a possible explanation for the referral of pain to the forehead and anterior scalp during attacks of migraine, and with arteritis and thrombosis involving vascular structures within the posterior fossa, the circle of Willis and the external carotid system of man.

Co-localization of retrogradely transported wheat germ agglutinin and the putative neurotransmitter substance P within trigeminal ganglion cells projecting to cat middle cerebral artery.

Neurons containing both wheat germ agglutinin (WGA) and substance P (SP) immunoreactivities were found in the ophthalamic division of the ipsilateral trigeminal ganglia following application of the axonally transported lectin WGA to cat middle cerebral artery. Immunohistochemistry was accomplished by staining for WGA and SP on adjacent sections by using the chromogen diaminobenzidine, or by staining on a single section with sequential application of WGA and SP antisera using the chromogens diaminobenzidine and 4-chloro-1-naphthol, respectively. These observations confirm the results of trigeminal lesion studies indicating that trigeminovascular projections to the middle cerebral artery in the cat contain the neurotransmitter SP. In addition, other neurotransmitters may be present in this pathway since less than 50% of WGA-labeled cells contained SP.