Antitumor efficiencies of monoclonal antibodies to connexin-43 second extracellular loop (MAbE2Cx43), temozolomide, and fractionated γ-irradiation in the monotherapy mode and in several optimized combinations were studied in Wistar rats with induced C6 glioma. The survival of animals with glioma and the dynamics of intracerebral tumor development were evaluated by MRT. Temozolomide monotherapy (200 mg/m(2)) and isolated radiotherapy in a total dose of 36 Gy shifted the survival median from 28 days (no therapy) to 34 and 38 days, respectively; 100% animals died under conditions of temozolomide monotherapy and radiotherapy. Monotherapy with MAbE2Cx43 in a dose of 5 mg/kg led to significant regression of the tumor (according to MRT data), cure of 19.23% animals with glioma, and prolongation of the survival median to 39.5 days after tumor implantation. Combined therapy with MAbE2Cx43 and temozolomide completely abolished the antitumor effect (survival median 29 days). Treatment with MAbE2Cx43 in combination with radiotherapy was associated with mutual boosting of the therapeutic efficiencies, leading to a significant inhibition of tumor development and prolongation of the survival median to 60 days. The mechanism of tumorsuppressive activity of the antibodies could be due to connexon blockade in Cx43-positive glioma cells in the peritumor invasion zone. Higher efficiency of combined therapy was presumably due to the increase in blood-brain barrier permeability for antibodies after irradiation of the brain and to additional inhibitory effect of antibodies towards radioresistant migrating glioma cells. The results suggested that MAbE2Cx43 could be effective as the first-line drug in combined therapy for poorly differentiated gliomas.

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To study demyelination and remyelination processes and their response to different drugs, a protocol for modeling multiple sclerosis using the copper chelator cuprizone was developed. Magnetic resonance imaging confirmed the presence of demyelination lesions on week 4 of 0.6% cuprizone-containing diet. Immunohistochemical staining with polyclonal antibodies to glial fibrillary acidic protein (pAb GFAP) confirmed the increase in the number of reactive astrocytes on week 4 of diet and during remyelination (week 2 after diet). Analysis of neurophysiological functions in mice with cuprizone-induced demyelination revealed motor and behavioral deficits. This model can be used as a tool for preclinical studies of the efficiency of multiple sclerosis diagnostic and therapy.

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