Sulforaphane-induced activation of the transcription factor NF-E2 related factor 2 (Nrf2 or the gene Nfe2l2) and subsequent induction of the phase II antioxidant system has previously been shown to exert neuroprotective action in a transient model of focal cerebral ischemia. However, its ability to attenuate functional and cellular deficits after permanent focal cerebral ischemia is not clear. We assessed the neuroprotective effects of sulforaphane in the photothrombotic model of permanent focal cerebral ischemia. Sulforaphane was administered (5 or 50 mg/kg, i.p.) after ischemic onset either as a single dose or as daily doses for 3 days. Sulforaphane increased transcription of Nrf2, Hmox1, GCLC and GSTA4 mRNA in the brain confirming activation of the Nrf2 system. Single or repeated administration of sulforaphane had no effect on the infarct volume, nor did it reduce the number of activated glial cells or proliferating cells when analyzed 24 and 72 h after stroke. Motor-function as assessed by beam-walking, cylinder-test, and adhesive test, did not improve after sulforaphane treatment. The results show that sulforaphane treatment initiated after photothrombosis-induced permanent cerebral ischemia does not interfere with key cellular mechanisms underlying tissue damage.

The CAD cell line is a variant of a CNS-derived Cath.a cell line established by targeted oncogenesis in transgenic mice. Cell differentiation of the cell line can be induced by "starvation," i.e., removal of serum from the culture medium (protein-free medium). The differentiated CAD cells extend long processes, which ultrastructurally contain abundant microtubules, intermediate filaments, and various synaptic vesicles/organelles in the varicose enlargements, thus resembling neurites. Histochemical studies demonstrated that the differentiated cells express a number of synaptic vesicle proteins, cytoskeletons, different neurotransmitter enzymes, neuropeptides, and glia proteins. The data suggest that the differentiated CAD cells may be a suitable model for studies of intraneuronal transport, recycling of receptors, and pharmacological investigations.

The CNS-derived cell line, CAD cell line, when grown in a protein free medium (PFM), differentiates to neuron-like cells with very long processes. It was previously studied biochemically and found to express TH activity, some neurospecific proteins, but no glial proteins. We have now further studied the CAD cells and focused on the expression of various neuropeptides, GAP-43 and GFAP. All peptides studied were present, including TH, but also GFAP, in contrast to earlier studies. A different kind of processes, short, slender and distributed like a "fringe" around cell body and along processes was observed, NESP55 but not other chromogranins was present in these "fringes", GAP43 showed some degree of overlapping with NESP55. The results show that even after differentiation in PFM, the CAD cells express a palette of neuropeptides and chromogranins, catecholaminergic markers as well as the glia-specific GFAP. Our efforts to induce exocytosis/endocytosis from the peptide granules by high K+ were, however, unsuccessful. Due to long processes, the CAD cells may represent a good model for studying intracellular transport, and, since the cells express both neuronal and glial characteristics, it may be useful for investigating the influence of different trophic/growth factors on the expression of various neuronal characteristics.

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Purpose Multiple sclerosis (MS) is a chronic progressive neurological disorder. Several environmental factors have been discussed as possible causing agents, e.g. organic solvents, whose impact on the disease is analysed in this review. Methods Systematic search strategies were used to identify high-quality studies of workers exposed to organic solvents, published up to September 30, 2019, in databases, such as PubMed, Cochrane library and Scopus. The exposure was in most studies obtained by questionnaires, supplemented with telephone interviews. The diagnosis MS was mainly detemined following a thorough neurological examination. Finally, fourteen case-control studies and two cohort studies met the inclusion criteria and were included in the meta-analysis. Random effects models were used to pool the results of the studies. Results The odds ratios from the 14 case-control studies included in the meta-analysis ranged from 0.12-4.0. Five casecontrol studies and one cohort study showed a significant association between the development of multiple sclerosis and exposure to organic solvents. The results from the other nine case-control studies and from one of the two cohort studies did not reach statistical significance. The pooled data from the 14 case-control studies gave an OR of 1.44 (95% CI 1.03-1.99), which shows a moderately increased risk of developing MS after exposure to organic solvents. Conclusions The final interpretation of the result is that organic solvents may be slightly associated with an increased risk to develop MS. In addition, other factors, e.g. genetic markers and smoking, may contribute to the development of the disease.