Biomedical subjects
Publications and source records attributed to L F Borges.
Normal host defense mechanisms are effective in preventing central nervous system (CNS) infection. Opsonins and compliment levels are normally low in the CNS, however. The relationship of these factors to CNS infection, specifically surgical wound infection and shunt infection, is discussed.
Normal structure and function of corneal epithelium is known to be related to proper innervation. To investigate possible trophic actions of sensory neurons on corneal epithelium, corneal innervation and various physical parameters were studied in normal rats and in rats treated as neonates with intraperitoneal injections of capsaicin. Corneal lesions were noted in treated rats which varied from multiple punctate areas of corneal opacity to deep stromal opacity with ulceration and neovascularization. These lesions waxed and waned throughout the animal's life. In addition, mechanical threshold of the corneal reflex was higher in capsaicin-treated rats. The tear rate in response to a provocative test was diminished in treated rats, presumably due to reduced afferent trigeminal input to the brain stem; blinking rates were more frequent in these animals. Using fluorescent retrograde tracing techniques, the number of cells innervating the cornea in capsaicin-treated rats was found to be significantly less compared with control animals. Innervation in the cornea (examined using a gold chloride technique) demonstrated a decrease in the number of corneal large axons in treated rats with neurite sprouting of these axons yielding a higher density of nerve fibers compared with controls. Thus, sprouting of residual sensory neurons occurs in response to the partial corneal denervation produced by capsaicin, and this sprouting does not functionally compensate to prevent the development of chronic keratitis.
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Two types of artificial membranes, a medical-grade aliphatic polyurethane and a polysiloxane-carbonate block copolymer, were tested as substitutes for dura in 24 and 12 rabbits, respectively. The films were placed either epidurally, subdurally, or as dural grafts in equal subgroups of animals. The postoperative course was uneventful with no manifestations of convulsive disorder or cerebrospinal fluid leak. The animals were sacrificed 3, 6, or 9 months after implantation of the artificial membranes. Both types of artificial membranes were easily removed from the underlying nervous and the other surrounding tissues. The histological examination failed to reveal adhesions, neomembrane formations, or any type of foreign body reactions to the polyurethane film. The implantation of the polysiloxane-carbonate film caused no reaction when it was applied epidurally. As a dural graft, the polysiloxane-carbonate copolymer induced the formation of a thin neomembrane of one to two layers of fibroblasts which formed a watertight seal of the dural defect. A similar thin neomembrane was found to encase this artificial membrane in the group of animals in which it was implanted subdurally. There was no foreign body reaction to the polysiloxane-carbonate film. The authors conclude that these materials hold promise as dural substitutes or in the prevention of spinal dural scarring, and should be evaluated clinically.
This study was undertaken to learn more about the keratitis that follows the neonatal administration of capsaicin to rats. In the first part of the study the density and pattern of corneal innervation were followed throughout postnatal development in litters of control rats and in rats that received capsaicin as neonates. In rats treated with capsaicin, the density of corneal innervation was lower than that of control rats until 28 days of age. Thereafter nerve fiber sprouting was observed within the corneas of capsaicin-treated rats. By 56 days of age the capsaicin-treated rats had a denser corneal innervation than did control rats. In the second part of the study the incidence and severity of the corneal trophic changes induced by capsaicin were studied in litters of rats treated with chronic tarsorrhaphy and in litters raised in the dark. Neither of these manipulations altered the incidence or severity of keratitis. These observations demonstrate that sprouting of the remaining corneal axons is related temporally to the previously observed decrease in keratitis. Furthermore the more severe keratitis observed in early postnatal life does not appear to be related to physical injury of the cornea.
Ranvier's method of staining tissue whole mounts with gold chloride to visualize nerve fibers was modified by lengthening the incubation time in gold chloride and reducing the time in acidulated water. These simple modifications of an old technique give consistent impregnation of nerve fibers with light background staining in whole mounts of cornea and dura.
Many fluorescent dye compounds are transported by axons in retrograde and anterograde directions. In the present study the uptake and retrograde axonal transport of 4 chemically related fluorescent dyes was evaluated in the peripheral nervous system of adult mice. Anterograde transport was studied in the corticospinal tract of adult rats. In addition to confirming the previously reported intra-axonal transport of Rhodamine-B-isothiocyanate, we report the transport of Rhodamine-X-isothiocyanate. Sulforhodamine-101-acid chloride and Lissamine rhodamine-B-sulfonyl chloride. By using the fluorescence intensity of the labeled motor and sensory neurons as well as cell counts of fluorescently labeled motor neurons and percent of labeled dorsal root ganglia (DRG) cells, we were able to quantitate the amount of retrograde transport of a given fluorescent compound. The two dyes with isothiocyanate groups available for conjugation were transported in higher amounts compared to the dyes containing sulfonyl chloride groups. No anterograde transport in the corticospinal system was observed. We conclude that the 4 dyes described are useful for retrograde neuroanatomical tracing experiments. We describe methods for quantifying the amount of retrograde transport by peripheral motor and sensory neurons.
The techniques of neural transplantation are almost 100 years old. As these techniques begin to be used to treat human neurological disorders, it is important to remember the contributions of the many investigators who have advanced this fascinating area of neurobiology.
This report describes a patient with communicating syringomyelia associated with enlarged cerebral ventricles who was managed by placing a ventriculoperitoneal shunt. His clinical improvement was rapid and dramatic. A comparison of preoperative and postoperative magnetic resonance scans documents shrinkage of the cervical syrinx.
The retrograde intraaxonal transport of several anthracycline antibiotics was assessed in the peripheral nervous system of adult mice. Despite certain chemical similarities, the intraaxonal transport of these molecules was variable and could be correlated with the structure of the aminosugar at the R-2 position. One particularly interesting compound, 4'-deoxydoxorubicin, was transported by dorsal root ganglia axons, but not by the axons of ventral horn neurons. These observations suggest that the sugar component of a molecule may be important for its intraaxonal transport in the peripheral nervous system.
The topography of choline acetyltransferase immunoreactivity was studied in the rat spinal cord with a monoclonal antibody. Cholinergic fibers were most prominent in lamina III of the dorsal horn and originated from cholinergic neurons within the spinal cord. Lamina X, which was rich in cholinergic neurons and fibers, provided cholinergic interconnections between the dorsal, intermediate and ventral gray. Within the ventral gray, choline acetyltransferase immunoreactive boutons were found on motor neurons. This study suggests that the cholinergic innervation of the spinal cord arises from neurons intrinsic to the spinal cord. The cholinergic neurons within the spinal cord may provide several, overlapping levels of regulation of spinal cord neurons.
Cerebellar Purkinje neurons accumulated propidium iodide, granular blue, and horseradish peroxidase conjugated to wheat germ agglutinin but not unconjugated horseradish peroxidase, bisbenzimide, or Evans blue when these compounds were infused into the lateral cerebral ventricles of awake, unrestrained rats. Accumulation of propidium iodide by Purkinje neurons of the vermis was associated with a reproducible behavioral abnormality characterized by truncal tremor, ataxia, and nystagmus. Both the accumulation of propidium iodide in Purkinje cells and the behavioral abnormality were prevented by prior intracerebroventricular administration of ouabain or colchicine, drugs that block neuronal transport processes. The ability of cerebellar Purkinje neurons to extract small and large molecules from the cerebrospinal fluid has important implications for their physiology and pathology.
Parenteral magnesium sulfate has been used to control acute convulsions of diverse etiologies and is currently a mainstay in controlling eclamptic convulsions. However, the site of this anticonvulsant action has remained controversial and not well studied in experimental epileptic models. Therefore we determined the effects of intravenously infused magnesium sulfate on the epileptic neural activity induced by topical application of penicillin G to motor cortex in anesthetized cats and dogs and in awake, undrugged primates. Magnesium sulfate was able to directly suppress neuronal burst firing and interictal EEG spike generation at serum levels below those producing paralysis. The degree of suppression corresponded to the serum magnesium concentration and was reversible. These results corroborate the clinical observations in patients that magnesium can produce an anticonvulsant effect apart from neuromuscular blockade and suggest it may have clinical applicability in treating a wider range of acute convulsions.