Johan Sjöstrand

Axonal uptake and retrograde transport of exogenous proteins in the hypoglossal nerve

Abstract Exogenous proteins (albumin labelled with Evans blue (EBA) and horseradish peroxidase) were injected into the tongue of various laboratory animals (rats, rabbits, mice and guinea pigs). At various time intervals thereafter the hypoglossal nuclei were examined with regard to the cytological localization of the tracers. In the hypoglossal neurones red fluorescent cytoplasmic were seen 10 h after injection of EBA into adult rats and rabbits indicating the presence of protein tracer. Peroxidase also accumulated in these neurones of suckling and adult mice and rats. The neuronal uptake of the protein tracers was blocked by crush injuries to the hypoglossal nerve and by arrest of blood circulation. Our results show that the hypoglossal neurones have the capacity to accumulate exogenous proteins after peripheral injection. This process must be a consequence of a fast retrograde axonal transport. As shown in previous studies, a similar transport also occurs in the peripheral motor neurones of the spinal cord in suckling mice. This phenomenon therefore exists in different species, ages and kinds of nerve.

Spread of herpes simplex virus in peripheral nerves

SummarySuckling mice were inoculated intradermally with herpes simplex virus into the sole of the hind foot. Titrations for infective virus from different levels of the sciatic nerve, dorsal ganglia, and spinal cord showed that virus was already present in the spinal cord two days after inoculation, and before virus could be recovered from the examined levels of the sciatic nerve. Ligatures, freezing, and local treatment with colchicine of the sciatic nerve could prevent the spread of infection. The ultrastructural features of nerves soaked with mitosis inhibitors are described. Extensive changes with ultimate collapse of axons and disintegration of myelin sheaths were found, while the Schwann cells showed no obvious degenerative changes and the endoneurial spaces were wide. It is considered that the infectious agent travels inside the axons to the CNS, and that a spread of virus in endoneurial spaces or by propagation in Schwann cells, as recently has been suggested, is of minor importance. The study seems to provide evidence that inside the axons a transport of materials directed disto-proximally all the way to the nerve cell body exists.ZusammenfassungSaugmäuse wurden intradermal in die Sohle des Hinterbeines mit Herpes simplex-Virus inoculiert. Titrationen auf das infektiöse Virus in verschiedenen Höhen des N. ischiadicus, der Dorsalganglien und des Rückenmarks zeigten, daß das Virus im Rückenmark schon 2 Tage nach der Inoculation, und ehe es in verschiedenen Abschnitten des N. ischiadicus nachgewiesen werden konnte, vorhanden war. Ligaturen, Durchfrieren und örtliche Behandlung des N. ischiadicus mit Colchicin konnte die Infektionsausbreitung verhindern. Die ultrastrukturellen Veränderungen der mit Mitosehemmern durchtränkten Nerven werden beschrieben. Es fanden sich starke Veränderungen der Axone mit schließlichem Kollaps sowie Desintegration der Markscheiden, während die Schwann-Zellen keine auffälligen degenerativen Veränderungen zeigten und die Endoneuralräume weit waren. Es wird angenommen, daß das infektiöse Agens innerhalb der Axone zum ZNS wandert und daß eine Ausbreitung des Virus, in den Endoneuralräumen oder in den Schwann-Zellen, wie es kürzlich vermutet worden war, von geringerer Bedeutung ist. Die Studie scheint den Nachweis zu erbringen, daß ein distoproximaler Materialtransport innerhalb der Axone bis zum Nervenzellkörper stattfindet.

Transport of labelled proteins in the optic nerve and tract of the rabbit

Abstract The transport of labelled material in the optic nerve and tract of the rabbit after an intraocular injection of [ 3 H]leucine has been studied. It was demonstrated that the precursor was incorporated into proteins, which were transported down along the axons of the retinal ganglion cells. Two migrating protein components are described. One with and average transport rate of 1.5–2 mm per day and a second very rapidly moving component with a transport rate of at least 110–150 m per day.

A longitudinal study of a population based sample of astigmatic children: II. The changeability of anisometropia

Abstract. The variability of anisometropi in a sample of 310 children with astigmatism at the age of 1 year was longitudinally studied during a 3‐year period between 1 and 4 years of age. The prevalence of anisometropia of 1 D or more at each year level was rather stable. When individual cases were examined we found that between the first and the last test session 19 of the 33 children with anisometropia at the first test session had become non‐anisometropic and were substituted with 14 new cases which were non‐anisometropic at the age of 1 year. In general, less than half of the cases, at all levels of anisometropia, remained anisometropic throughout the whole test period. We also found that children with anisometropia persisting through the whole test period were at considerable risk, about one out of four, of developing amblyopia. There was no simple relationship, however, between anisometropia at a certain age level between 1 and 4 years and amblyopia and/or strabismus. Non‐persisting anisometropia in an emmetropizing eye is in most cases a benign sign and not connected with an increased risk for developing amblyopia.

Contrast sensitivity in macular disease. A preliminary report.

Psychophysical measurements of contrast thresholds for sinusoidal gratings of variable frequency were made in normal controls and in patients with macular disease. Normal controls showed a U‐shaped contrast sensitivity function comparable with previous reports. Patients with relatively well conserved visual acuity showed a marked impairment in contrast sensitivity for targets of high and intermediate spatial frequencies, while patients with more advanced disease showed a pronounced impairment across a larger spectrum of frequencies. Our findings provide insight into the visual difficulties of daily life of patients with macular disease. The determination of contrast sensitivity seems to be an important and very sensitive tool for the detection of early disturbances.

Risk factors in amblyopia.

Any intervention to prevent serious amblyopia is based on the knowledge about normal versus subnormal visual development. Our ability to predict with high degree of certainty which children will develop amblyopia will be dependant on the characteristics of various risk factors for initiating the development of squint or amblyopia. We have used longitudinal studies of population based cohorts of young children to define some of these risk factors such as refractive errors. Three hundred and ten children with an astigmatism 1.0 D at one year of age were refracted yearly between the age one and four years. Astigmatism and anisometropia were found to be highly variable during infancy and early childhood. Longitudinal follow-up seems to be needed to separate the normal from the abnormal refraction development, which initiates the development of the amblyopia. Children with constant or increasing astigmatism or anisometropia between one and four years were ‘at risk’.In parallel we have studied important factors for successful treatment of amblyopia. Based on these findings we conclude that a population screening at four years of age seems to be advantageous in Sweden in order detect and successfully treat most cases of amblyopia.

Fast and slow components of axoplasmic transport in the hypoglossal and vagus nerves of the rabbit

Summary The axonal transport of labelled proteins was studied in vagus and hypoglossal nerves of rabbits after an intramedullary injection of [ 3 H]leucine. Two migrating protein components were described. The rapid component moved at a rate of about 400 mm/day and 300 mm/day and the slow component at an average rate of 26 mm/day and 5 mm/day in the vagus and hypoglossal nerve respectively. Cell fractionation studies of the nerves showed that the rapidly migrating component was largely associated with the particulate fraction with the highest specific radioactivity in the microsomal fraction. In the slow component the highest specific activity was found in the soluble protein fraction. The effect of Triton-X-100 on the subcellular distribution was discussed.

A longitudinal study of a population based sample of astigmatic children. I. Refraction and amblyopia.

Abstract. The refraction changes in 310 children with astigmatism ≥ 1.0 D in at least one eye at one year of age were followed during a period of 3 years. At the age 4 years amblyopia was found in 23 children (7%). The refraction data of these children were compared to the rest of the sample. We found that an increasing astigmatism during the test period was associated with an increased risk to develop amblyopia. The majority of children (n = 280) showed a decrease of their astigmatism, whereas all cases with a marked amblyopia (V. A. < 0.5) or binocular amblyopia, except one, had an increasing or unchanged astigmatism during the age period 1 to 4 years. Strabismus and oblique astigmatism at any time during the test period was also strongly related to amblyopia. The incidence of strabismus (1%) was unexpectedly low. The study also showed that independent of age there was no simple relationship between amblyopia and refraction errors measured at a single test session. The main conclusion of this study is that failure of emmetropization may play an important role in visual development.

Changes in fast axonal transport during experimental nerve compression at low pressures

The minimal pressure for impairment of fast anterograde axonal transport was determined in rabbit vagus nerve. Proteins, transported by fast anterograde axonal transport, were labeled by a microinjection of [3H]leucine into the nodose ganglion, and a small compression chamber was applied around the cervical vagus nerve. In this way the nerve was subjected to acute, graded compression. Compression at 20 mm Hg for 2 h as well as sham compression did not induce accumulation of axonally transported proteins at the level of compression. However, a pressure of 30 mm Hg for 2 h induced a block of axonal transport at the site of compression. The causes of the axonal transport block are discussed as well as the minimal pressure level in relation to pressures found in clinical nerve compression lesions.

Neuroglial proliferation in the hypoglossal nucleus after nerve injury

Abstract After injuring the hypoglossal nerve the neuroglia cell reaction was studied in the region of the neuronal perikarya in the hypoglossal nucleus of both rabbit and mouse. Radioautography was used to determine the rate of cell proliferation; it was demonstrated that 3H-thymidine could serve as a precursor for DNA synthesis for more than 2 hr after intracisternal injection of it in the rabbit. The labeled neuroglia cells in the regenerating hypoglossal nucleus of the rabbit were predominately microglial from 2 hr up to 3 weeks after isotope injection. The life-span for a large part of the labeled cells was at least 3 weeks. After nerve section the neuroglial proliferative response was more marked than after a single crushing, whereas no additional proliferative reaction could be observed in the rabbit after a repeated crushing either 14 or 49 days after the initial injury. In contrast to the almost complete survival of nerve cells and reversibility of the astrocytic hypertrophy after crushing the hypoglossal nerve, nerve section gave a 10% reduction in number of nerve cells and a persistent astrocytic hypertrophy for at least 3 months. A marked neuroglial proliferation was found on the 2nd and 3rd day after crushing the mouse hypoglossal nerve. No labeled cells were demonstrated in the vascular walls, as was the case in the rabbit. No evidence for a hematogenous source of these proliferating cells could be obtained in mice given closely repeated injections of 3H-thymidine to label leucocytes.