Audiogenic epilepsy in mice with different genotypes after neonatal treatments enhancing neurogenesis in dentate gyrus.

Pups of Wistar and KM rats (with predisposition to audiogenic epilepsy) were daily injected with neuropeptide semax (50 mg/kg) or NO-synthase inhibitor L-NAME (50 mg/kg) on days 7-11 of life. Alterations of audiogenic seizures pattern were revealed in rats of both strains at the age of 1 month, while changes in seizure severity were genotype-dependent. Both agents enhance neurogenesis in the dentate gyrus of the hippocampus and the delayed effect in the form of altered seizure pattern seems to be determined by this factor. Genotype-dependent alterations of seizure severity after administration of semax and L-NAME were differently directed. These effects are suggested to be underlined by physiological and biochemical mechanisms not related to the intensity of postnatal neurogenesis.

Cell-based therapy of chronic degenerative diseases of the central nervous system.

The traditional methods of pharmacotherapy of the degenerative diseases of the central nervous system do not frequently allow one to achieve the desired clinical effect. The fundamentally new approach for the treatment of severe neurological diseases is provided by the methods of biological medicine, in particular, transplantation of a complex of fetal tissues. Cell-based therapy was used to treat patients with multiple sclerosis; ante-, intra- and postnatal lesions; consequences of hemorrhagic and ischemic apoplexies; neuritis of facial nerve; sclerosis; Parkinson's disease; Alzheimer's disease; epilepsy and other types of pathologic process. The source material for obtaining a suspension of cells was the fetuses of allogenic origin. The suspension of brain cells in amounts of up to 1.5 x 10(8) cells and vitality not less than 40% was administered to the patients into liquor spaces using the method of endolumbar puncture. The total number of transplantations was 1900. Practically in all the cases FT was tolerated well. Positive clinical and immunologic changes were observed in the majority of the patients, thus, remission induction (in the patients with the progressive course of multiple sclerosis) for a period over 12 months was registered in 87.5% of the cases. Noteworthy that considerable changes were observed in immunograms: depression of antibody levels to brain-specific proteins, native and denatured DNA; quantitative and qualitative improvement of lymphocyte subpopulation indices, positive changes in the immunoregulatory index. Clinically, in 69% of the cases there was an improvement in more than one neurological defect and a change in the values of the Kurtzke scale towards a decrease by 2-3 points. The conduct of cell therapy with the MS patients under the acute process conditions after liquorosorption allowed the arresting of clinical manifestations and the creation of preconditions for further restoration. The retrobulbar transplantations provided a quick arrest of the retrobulbar neuritis clinical symptoms and in one case an almost complete restoration of vision in the patient with amaurosis (blindness). The remission duration has a marked direct dependence on the number of courses of endolumbar transplantations. Thus, the method of cell therapy with the use of human tissue transplantations is safe and can be used for different neurodegenerative lesions of the central nervous system. The high efficacy of the method suggests the possibility and necessity of using this method as an alternative of classical pharmacological therapy. An important element of cell therapy is the control after the state of the patient's immunity system.

Xenografts of embryonic nerve tissue from Drosophila neuromutants stimulate development of neural homografts in rat brain and block glial scar formation.

The influence of xenografts of Drosophila melanogaster embryonic nerve cells on the development of embryonic neurohomografts in the adult rat brain has been investigated. Embryonic nerve cells, marked with bacterial galactosidase gene (lacZ) from D. melanogaster strain with a mutation in the Delta locus, were transplanted into adult rat brain. Drosophila cells were easily identifiable in brain histological sections by X-gal staining. Xenografts survived for at least 2-3 weeks in the recipient brain after the operation to be subsequently attacked by macrophages. Importantly, no glial scar was formed around the xenograft. The addition of Drosophila embryonic nerve cells to a homograft of rat embryonic neural tissue facilitated the survival and development of this homograft by blocking the glial scar formation, stimulating vascularization of the graft area and differentiation of the implanted embryonic nerve cells.