Arie Solomon

Tumor necrosis factor facilitates regeneration of injured central nervous system axons

The results of this study attribute to tumor necrosis factor (TNF) a role in regeneration of injured mammalian central nervous system (CNS) axons which grow into their own degenerating environment. This is the first time that a specific factor involved in axonal regeneration has been identified. The axonal environment is occupied mostly by glia cells, i.e., astrocytes and oligodendrocytes. Previous studies have shown that mature oligodendrocytes are inhibitory to axonal growth. Therefore, it seemed likely that application of a factor such as TNF, which has been shown to be cytotoxic to oligodendrocytes, would contribute to the creation of permissive conditions for axonal regeneration. In the present work, injured adult rabbit optic nerves were treated with human recombinant TNF (rhTNF). As a result, abundant newly growing axons (circa 9000, about 4% of the total estimated number of axons in an intact adult rabbit) were observed traversing the site of injury.

Temporal parameters of low energy laser irradiation for optimal delay of post-traumatic degeneration of rat optic nerve

Compression injury of a central nerve results in its degeneration with irreversible loss of function due to the inability of the mammalian central nervous system (CNS) to regenerate. In contrast, the CNS of lower vertebrates has a high capacity to regenerate. Recently, low energy laser irradiation was shown to attenuate degeneration in injured CNS nerves. The optic nerves of rats were subjected to moderate crush, calibrated so that some electrophysiological activity was preserved. The nerves were then subjected to low energy laser irradiation (10.5 mW, 2 min daily) for various periods. The electrical activity of the nerves, distal to the site of injury, was determined by measuring the compound action potential at the termination of the experiment. Two weeks of irradiation begun immediately after injury and continued daily thereafter, resulted in a compound action potential which was significantly higher (mean +/- S.E.M. 1856 +/- 535 microV) than that of non-irradiated injured nerves (351 +/- 120 microV). The effect was temporary and subsided within a week. This two-week irradiation was slightly more effective than a treatment lasting one week (1406 +/- 225 microV) and was significantly more effective than 4 days of irradiation (960 +/- 133 microV). The number of treatments is therefore important. The time at which the treatment commences relative to the injury is also critical. Irradiation initiated two hours after the crush was about half as effective as immediate irradiation (810 +/- 42 microV). No apparent effect was evident when the laser was applied for the first time 5 h, or longer, after the crush.(ABSTRACT TRUNCATED AT 250 WORDS)

Disappearance of astrocytes and invasion of macrophages following crush injury of adult rodent optic nerves: Implications for regeneration

Injury to the mammalian central nervous system results in loss of function because of its inability to regenerate. It has been postulated that some axons in the mammalian central nervous system have the ability to regenerate but fail to do so because of the inhospitable nature of surrounding glial cells. For example, mature oligodendrocytes were shown to inhibit axonal growth, and astrocytes were shown to form scar tissue that is nonsupportive for growth. In the present study we report an additional phenomenon which might explain the failure of axons to elongate across the site of the injury, namely, the absence of astrocytes from the crush site between the glial scar and the distal stump. Astrocytes began to disappear from the injury site as early as 2 days after the injury. After 1 week the site was necrotic and contained very few glial cells and numerous macrophages. Disappearance of glial cells was demonstrated in both rabbit and rat optic nerves by light microscopy, using antibodies directed against glial fibrillary acidic protein, and by transmission electron microscopy. Results are discussed with reference to possible implications of the long-lasting absence of astrocytes from the injury site, especially in view of the differences between the present findings in rodents and our recent observations in fish.

A graded work site intervention program to improve sun protection and skin cancer awareness in outdoor workers in Israel

AbstractObjectives: A graded worksite intervention program to improve sun protection and skin cancer awareness of outdoor workers was implemented and evaluated longitudinally over a period of 20 months. Methods: Outdoor male workers (144/213 recruits) from geographically separated units of the Israel National Water Company were allocated to complete (n = 37), partial (n = 72) or minimal (n = 35) intervention groups. Subsequent to the assignment and training of local safety officers, an educational and medical screening package was provided to the corresponding groups either once, or repeatedly a year later. Personal sun protective gear was provided upon repeated intervention. Outcome measures were evaluated through self-response questionnaires administered prior to the first intervention pulse, and 8 months after the first and second interventions. Results: A 15–61% improvement in sun-protection habits was noted in the entire study population 8 months after initialization, compared to no sunscreen use, 20% sun-exposed skin area and highest mean occupational exposure dose of 1.68 MED/day at pre-test. An even greater use of sunscreen was evident 1 year later in the complete and partial intervention groups, + 80% and + 52%, respectively. The baseline rate of self-examination of the skin in the same two groups (49%) increased significantly at post-test (+ 71% and + 53%, respectively). Conclusions: This integrated intervention program led to significantly improved sun protection and skin cancer awareness. Repeated intervention combined with the supply of sun-protective gear contributed to an even greater impact.

Increased electroretinogram a-wave amplitude after intravitreal bevacizumab injection for neovascular age-related macular degeneration.

Purpose:  To assess the effect of bevacizumab (Avastin®), a vascular endothelial growth factor inhibitor, on retinal function by full‐field electroretinography (ERG) in patients with neovascular age‐related macular degeneration (AMD).

Glial-Derived Substances Associated with CNS Regeneration

Axonal injury stimulates two complimentary systems, the axon and its surrounding non-neuronal cells which operate in synchrony. Our results suggest that the non-neuronal cells response to injury have an impact on the subsequent ability of the axon to grow and elongate. In this chapter we review some of our observations related to the components which interplay in this process. One example for biochemical manifestations of an early response to injury in CNS of a regeneration system (i.e. fish visual system) is the accumulation of a 28 kDa polypeptide which we identified as apoli- poprotein-A-I (apo-A-I). The accumulation of primarily one isoform of apo-A-I, may be due to a need created by the injury for a particular stable and functional isoform. These observations are similar to those reported in adult rat sciatic nerves where a 37 kDa polypeptide showed an elevation after injury and was identified as apo-E. We attribute to apo-A-I a role in removal of dead tissue to pave the way for regeneration. Subsequent regeneration depends on the accessibility to growth supportive substances and organized and proper extracellular matrix. We found that soluble substances originating from regenerating fish optic nerves and newborn rabbit optic nerves contain factors which activate neurons and may modulate the glial response to injury. These factors when applied to injured adult rabbit optic nerves cause in the later biochemical alterations in the retinas and acquisition of a growth supportive surface including accumulation of laminin by the surrounding nonneuronal cells. A non-regenerative system either does not provide these factors, or keeps them inaccessible at the critical time but has the machinery to respond to these factors. Our results suggest that the response to injury of non-neuronal cell is not different from the response to injury of any other damaged tissue and may therefore obey to the same set of rules governing proliferation and differentiation of other cells. The possible involvement of proto- oncogenes in their response to injury was therefore examined. The protooncogenes fos and myc were found to be constitutively expressed in these cells and an elevation was found after injury. These protoncogenes may have a role in the plasticity of this system, an issue which is currently being further investigated.