Membrane changes during hibernation.
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Animals↗
Biomedical subjects
N A Azzam
Publications and source records attributed to N A Azzam.
Host nerve fibers that regenerate and reside long-term in a rejected nerve allograft are not protected by permability barriers.
We investigated whether permeability barriers develop and protect host nerve fibers that regenerate and reside long-term in a rejected nerve allograft. In order for the barriers to form, host cells have to enter the rejected allograft and differentiate into new endothelial and perineurial cells that respectively form the impermeable endoneurial blood-nerve and the perineurium-nerve barriers that are present in normal nerve. A 2-cm long graft of peroneal nerve was taken from American Cancer Institute (ACI) or Fischer (FR) rats and transplanted to bridge a 2-cm gap between the cut ends of the peroneal nerve of other FR rats. Six months postoperatively, histology revealed that regenerated host nerve fibers in ACI allografts were compartmentalized into numerous minifascicles by perineurial cells and that blood vessels were located outside rather than inside the perineurial compartments among the nerve fibers. Administration of the permeability indicator horseradish peroxidase to allograft recipients (intravenously or topically to the graft in situ) revealed that it entered the endoneurium of microcompartments and spread around the nerve fibers. In contrast, none of the indicator reached nerve fibers in FR syngrafts or normal ACI or FR nerves which were not microcompartmentalized. We concluded that host nerve fibers that regenerate and reside long-term in a rejected nerve allograft are not protected by permeability barriers.
Animals↗
The loss of regenerated host axons in nerve allografts after stopping immunosuppression with cyclosporin A is related to immune effects on allogeneic Schwann cells.
After immunosuppressive therapy with Cyclosporin A (Cy-A) is stopped, nerve allograft rejection occurs. In addition to the loss of allogeneic perineurial, vascular, and Schwann cells, host axons that regenerate into the allograft disappear despite the fact that the axons are not foreign tissue. The present experiment was performed to correlate immune events and allogeneic cell and host axonal loss in nerve allografts after terminating Cy-A treatment. Nerve grafts (4 cm long) were taken from American Cancer Institute (ACI) rats and joined to the peroneal nerves of Fischer (FR) or ACI rats that received a daily dose of Cy-A (10 mg/kg, intraperitoneally). After one week, Cy-A therapy was stopped and the grafts were examined 2-6 weeks postoperatively by light and electron microscopy. No immune reaction nor destruction of perineural, vascular, or Schwann cells was found in 2- or 3-week-old allografts (i.e., ACI to FR grafts). These grafts underwent Wallerian degeneration and were invaded proximally by regenerating host axons, some of which were thinly myelinated. At 4 weeks, the perineurium of each allograft became infiltrated by mononuclear cells and was destroyed. Many of the endoneurial blood vessels of these grafts were occluded and their endothelial cells were degenerating or missing. Despite the immune reaction, allogeneic Schwann cells remained and continued to myelinate or ensheath host axons that had now grown up to 3 cm into the grafts.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The fate of cryopreserved nerve isografts and allografts in normal and immunosuppressed rats.
Donor Schwann cells, perineurial cells, and vasculature are known to survive in grafts of peripheral nerve. In the present study, we attempted to cryopreserve nerve to determine whether these cellular components of nerve would survive after transplantation and support host axonal regeneration through the graft. Four-centimeter lengths of peroneal nerves were removed from inbred adult American Cancer Institute (ACI) rats and placed into vials that contained a cryoprotective mixture of dimethyl sulfoxide and formamide (DF) at room temperature. Each vial with nerves in DF was cooled at a rate of 1-1.5 degrees C/minute down to -40 degrees C at which point the vials were plunged into liquid nitrogen at -196 degrees C. After 5 weeks of storage, the nerves were thawed and DF removed. Some of the cryopreserved-thawed ACI nerves were transplanted as isografts into the legs of ACI rats. Other ACI nerves were used as allografts and inserted into immunologically normal Fischer (FR) rats that were untreated or were immunosuppressed with the drug Cyclosporin A (Cy-A). At surgery, only one end of the nerve graft was joined to the cut proximal end of the peroneal nerve of the host. The cellular elements of ACI grafts were present at 5 weeks in grafts removed from ACI rats and FR rats treated with Cy-A. Non-immunosuppressed FR rats rejected ACI nerves as did FR rats in whom Cy-A was stopped after 5 weeks of treatment. All surviving ACI grafts underwent Wallerian degeneration and consisted of columns of Schwann cells, which in their proximal portion were associated with regenerating host axons. The donor perineurial sheath and vasculature were also present in surviving grafts. ACI isografts only were examined 20 weeks postoperatively. All normal tissue components survived in these older grafts and contained regenerated and myelinated host axons throughout their 4 cm lengths. These results demonstrated that the cellular elements of nerve can be cryopreserved, and after transplantation, survive and function. Because nerves survived after prolonged cryopreservation, it seems feasible to establish a nerve bank from which grafts can be withdrawn to repair gaps in injured nerves. However, cryopreserved nerves used as allografts remain immunogenic and require immunosuppression for their survival.
Animals↗
Regenerating axons are not required to induce the formation of a Schwann cell cable in a silicone chamber.
After suture of proximal and distal nerve stumps into the ends of a silicone chamber, a tissue cable forms inside the chamber through which axons regenerate. Schwann cells are a critical cellular component of the cable because in their absence axons fail to regenerate into the cable. In this study, we sought to determine whether axons were needed to induce the formation of a Schwann cell-containing cable. Transected stumps of sciatic nerves of adult rats were sutured into the ends of silicone chambers prefilled with phosphate-buffered saline or dialyzed plasma, leaving a 10-mm interstump gap. In order to eliminate any axonal influence in the chamber, the proximal sciatic nerve was further transected, ligated, and reflected, leaving a 4-mm piece of denervated nerve in the proximal chamber. A tissue cable formed at 4 weeks only in those chambers prefilled with dialyzed plasma. Light and electron microscopy revealed a central core of Schwann cells and fibroblasts within the cable that were collectively surrounded by a circumferential layer of fibroblasts and collagen. Blood vessels were randomly located throughout the cable. The Schwann cells extended numerous processes that were confined within a basal lamina-like membrane. Many of these processes contained microtubules and resembled unmyelinated axons. The ultrastructure of the processes, however, differed from that of axons in that some of the processes were in direct contact with the basal lamina of the Schwann cells and not surrounded by any other cell extensions. However, since these processes neither stained with silver nor disappeared after transection of the nerves entering or leaving the chamber, we conclude that they are not axons but in fact Schwann cell processes. In other animals bearing 4-week cables, the reflected nerve stump was reattached to the nerve piece in the proximal end of the chamber. Four weeks later, all the cables and varying lengths of the distal nerve trunks were filled with numerous myelinated and unmyelinated axons. The Schwann cell cable that forms within a dialyzed plasma prefilled chamber presents a useful system for basic research concerning the molecular mechanisms of Schwann cell or Schwann cell-axonal interactions and for applied research involving the clinical repair of human peripheral nerve injuries. Since a cable formed by our surgical method supports axonal regeneration, it has the potential to eliminate the need for a nerve graft to repair a gap in a nerve that requires delayed surgical intervention.
Animals↗
Observations on the blood and perineurial permeability barriers of surviving nerve allografts in immunodeficient and immunosuppressed rats.
The authors investigate whether there are any permeability changes in the endoneurial blood-nerve barrier and the perineurium-nerve barrier of surviving nerve allografts. In a normal nerve, the blood-nerve barrier regulates the passage of substances from endoneurial blood vessels into the endoneurium, whereas the perineurium-nerve barrier protects the endoneurium from agents that escape from permeable epineurial vessels and accumulate around the nerve. Nerves from ACI rats were transplanted into immunologically deficient nude rats or normal Fischer rats immunosuppressed with cyclosporin A. None of the nerve allografts was rejected. The blood-nerve barrier of nerve allografts at 2 and 6 weeks postoperatively was permeable to intravenously injected horseradish peroxidase, which spread into endoneurial tissue. Electron microscopy revealed that horseradish peroxidase escaped from endoneurial vessels through intercellular junctions between endothelial cells. At 24 weeks, the blood-nerve barrier of nerve allografts had recovered and the endoneurial vessels, like those in normal nerves, were impermeable to horseradish peroxidase. The perineurium-nerve barrier of nerve allografts remained impermeable to horseradish peroxidase at all times. Axons were grouped into numerous minifascicles at nerve anastomosis zones at 24 weeks. Each nerve fascicle was surrounded by an impermeable perineurium. These results demonstrate that regenerated axons in long-term surviving nerve allografts and at anastomosis zones are protected by permeability barriers. It is concluded that permeability barriers of nerve allografts are not permanently altered by a foreign environment (grafts to nude rats) even when immunosuppression with cyclosporin A is required to prevent allograft rejection (grafts to Fischer rats).
Animals↗
Nerve cables formed in silicone chambers reconstitute a perineurial but not a vascular endoneurial permeability barrier.
The passage of molecules into the endoneurial environment of the axons of normal peripheral nerve is regulated by two permeability barriers, the perineurial-nerve barrier and the endoneurial blood-nerve barrier. These barriers exist because of the presence of tight junctions between adjacent perineurial cells and adjacent endothelial cells. In the present study we investigated whether permeability barriers form in nerve cables, which develop inside silicone chambers. The sciatic nerves of adult rats were cut, and the proximal and distal ends sutured into opposite ends of silicone chambers that were filled with dialyzed plasma. The presence of barriers was determined with the tracer horseradish peroxidase (HRP), which was injected intravenously and detected histochemically in tissues by light and electron microscopy. At four weeks, a regenerated nerve cable extended across the 10 mm length of each chamber. However, no permeability barriers were present since the reaction product for HRP was visible throughout the cable. At twenty-six weeks, all the axons in cables were gathered into minifascicles. Each minifascicle of axons was surrounded by perineurial cells. Blood vessels were excluded from the minifascicles by the perineurial cells and the vessels were permeable to HRP, thus indicating that their endothelial cells had not formed tight junctions. Despite the leakage of HRP from the excluded vessels, the tracer did not reach the axons because the perineurial cells encircling the minifascicles developed tight junctions. In some animals, the chambers were removed at four weeks to determine whether the chamber influenced barrier development. This manipulation had no effect since cables, with or without chambers, exhibited similar findings at twenty-six weeks. Our results indicate that nerve cables regenerate a perineurial but not an endoneurial permeability barrier. We conclude that axons in long-term cables are protected by only a perineurial permeability barrier.
Animals↗
Regeneration of central nervous system axons into an acellular tube in the absence of distal tissue.
To differentiate between local and distant influences on central nerve regeneration, an impervious, stainless-steel cannula, 12 mm long, was placed in the path of severed axons within the corpus callosum of adult rats. The cannula was occluded for 1 week after implantation to prevent herniation of tissue into its lumen. The extracranial end of the tube was plugged with Gelfoam rather than tissue. Inflammatory cells within the tube decreased in number with time and all animals survived for the experiment's duration of 4 to 16 weeks. Some callosal axons grew into the cannula and eventually extended about 1.3 mm. After 8 to 16 weeks, the lumen of the cannula contained many unmyelinated axons, some of which formed fascicles, myelinated axons, demyelinating axons, a few oligodendrocytes, and many astrocytic processes, macrophages, and blood vessels. A striking feature was the linear orientation of cells and their processes. The distal tip of the core resembled a central nervous system explant: it included an appreciable number of growth cones, synaptic terminals embedded in a generous extracellular space, and occasional remyelinating axons. Thus, within an impervious, acellular conduit and in the absence of distal tissue, intrinsic, neuronal processes can be redirected, fasciculate, myelinate, and can regrow alongside glia and endothelium. An indwelling tube, isolating the growth from surrounding brain fluid, may permit assessment of glial, neuronal, and extracellular contributions to the directed regeneration of adult, central axons.
Animals↗
Spontaneous spongy degeneration of the mouse brain.
A spontaneously-occurring spongy disorder of the white matter of the central nervous system was discovered in the Charles River strain of Swiss-Webster mice and is described in this report. The disorder was transmitted with an autosomal recessive pattern of inheritance. Clinical characteristics of the affected animals included enlargement of the cranium, failure to thrive and tremor of the hind limbs when held by the tail in a suspended position. Maintenance of the colony with propagation of the disease was achieved by selective in-breeding of litter mates. Light microscopic examination of the central nervous system revealed a spongy degeneration of the white matter of the entire neuraxis. Ultrastructural studies localized the abnormality to the cell body and processes of the astrocyte which appeared distended and enlarged with dispersion of cytoplasmic organelles. Hemidesmosomes were prominent in the foot processes of astrocytes. This animal model bears a similar morphology and pattern of inheritance to Canavan's spongy degeneration of the white matter in humans and should provide a base for future investigations aimed at gaining insight into the pathogenesis of the human and this animal neurological disorder.
Animals↗
Changes in the surface fine structure of rat third ventricular ependyma following chronic acetazolamide treatment.
Participation of non-choroidal elements, particularly of ventricular ependyma, in CSF production is well recognized. The present investigation is an attempt to elucidate possible surface changes in the ventricular lining following chronic acetazolamide administration in the rat. A progressive time-dependent change was observed in the ependyma of the third ventricle. In the dorsal ciliated zone the appearance of dilatations and surface evaginations on cilial shafts were the predominent features. The ventral non-cilated area was characterized by eruption of blebs and microvilli with apical swellings. The significance of these surface fine structural changes are discussed in the light of available studies. It appears that the ependyma is stimulated into increased activity. However, the precise nature of such a response--whether secretory or absorptive--must remain conjectural until correlative scanning and transmission electron microscopic data become available.
Acetazolamide↗
Anatomical characteristics of palatoglossus and the anterior faucial pillar.
Palatoglossus and the anterior faucial pillar were studied using three techniques: 1) gross dissection, 2) radiographic filming, and 3) histological sectioning. The total subject sample included 25 normal adult male and female cadavers. Palatoglossus has a flattened belly within the faucial pillar, a fan-shaped termination within the palate, and a vertical tapering termination within the tongue. The region of attachment into the palate differs among individuals which could influence its relative importance in velar versus lingual movement. The pillar contains a large investment of loose connective tissue which also penetrates palatoglossus. The collagenous framework would apparently allow expansion of the pillars but also prevent rupture of the tissue at extreme extension. The anterior portion of the pillar contains a sheath of elastic fibers with a density gradient increasing from the tongue to the soft palate. The elastic fibers, which also intermingle with palatoglossus fascicles, could provide a restorative force in lowering the palate, helping to keep the nasopharyngeal airway patent.
Adult↗
Changes in the surface of fine structure of choroid plexus epithelium following chronic acetazolamide treatment.
Surface changes in the epithelium of the choroid plexuses of the lateral and third ventricles of rats induced by chronic administration of acetazolamide have been studied by scanning electron microscopy. After 3 weeks atrophic changes were evident, the microvilli and blebs normally seen on the ventricular surface of the cells appeared attenuated, and in extreme cases they disappeared, leaving the cell surface completely denuded. Localized areas of hypertrophy, indicated by secondary spherical budding, were occasionally observed. The atrophic changes accord with the known inhibitory effects of acetazolamide on CSF formation: perhaps the small number of cells undergoing hypertrophy compensate to some extent for the atrophic ones and maintain some CSF secretion.
Acetazolamide↗
The morphology of musculus uvulae.
The morphology of the musculus uvulae was studied utilizing detailed gross anatomical dissection and histological sectioning of the soft palate in seven adult human cadavers. The results indicated that the musculus uvulae is paired as previously described in most anatomy texts. Each bundle takes origin lateral to the midline from the tendinous palatal aponeurosis posterior to the hard palate and just anterior to the insertion of the levator veli palatini muscle. The two bundles converge in an area overlying the sling of the levator muscle and course along the dorsum of the soft palate terminating as two separate bundles which subdivide and insert between the mucous glands of the uvula proper into the connective tissue and basement membrane of the mucosa. Becuase of its location and size, it appears that contraction of the musculus uvulae would add bulk to the dorsal surface of the elvated soft palate thus aiding in occlusion of the velophryngeal portal during speech and deglutition.
Aged↗
The morphology of musculus uvulae.
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Humans↗
Protein catabolism in young mice following whole-body x irradiation.
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Animals↗