Perturbed Ca2+-dependent signaling of DYT2 hippocalcin mutant as mechanism of autosomal recessive dystonia.

A recent report of autosomal-recessive primary isolated dystonia (DYT2 dystonia) identified mutations in HPCA, a gene encoding a neuronal calcium sensor protein, hippocalcin (HPCA), as the cause of this disease. However, how mutant HPCA leads to neuronal dysfunction remains unknown. Using a multidisciplinary approach, we demonstrated the failure of dystonic N75K HPCA mutant to decode short bursts of action potentials and theta rhythms in hippocampal neurons by its Ca2+-dependent translocation to the plasma membrane. This translocation suppresses neuronal activity via slow afterhyperpolarization (sAHP) and we found that the N75K mutant could not control sAHP during physiologically relevant neuronal activation. Simulations based on the obtained experimental results directly demonstrated an increased excitability in neurons expressing N75K mutant instead of wild type (WT) HPCA. In conclusion, our study identifies sAHP as a downstream cellular target perturbed by N75K mutation in DYT2 dystonia, demonstrates its impact on neuronal excitability, and suggests a potential therapeutic strategy to efficiently treat DYT2.

[IMPACT OF XENOTRANSPLANTATION OF NEUROGENIC STEM CELLS IN COMPLEX WITH THE TISSUE MATRIX NEUROGELTM ON RESTORATION OF MOTOR FUNCTION OF A RAT SPINAL CORD AFTER EXPERIMENTAL SPINAL TRAUMA].

The method of restorative treatment for experimental spinal cord trauma (SCT), using implantation of synthetic matrix in combination of neurogenic stem cells, was introduced. Motor function of posterior іpsilateral extremity (PIE) was estimated in accordance to Basso­Beattie­Bresnahan (ВВВ) scale. Application of the method proposed have promoted essential enhancement of early neuroprotecting impact of the implanted NeuroGelTM, reducing time of early restoration of the PIE function.

[THE IMPACT OF XENOTRANSPLANTATION OF NEUROGENIC STEM CELLS IN COMPLEX WITH THE TISSUE MATRIX NEUROGELTM ON THE POSTTRAUMATIC SPASTICITY SYNDROME COURSE IN EXPERIMENT].

The impact of implantation of synthetic matrix NeuroGelTM together with neurogenic stem cells (NSC) on the course of posttraumatic spasticity syndrome was studied. Тhe laboratory animals were white mongrel male rats (5 mo, 250 g); the trauma simulation ­ transsection of the left half of spinal cord (SC) on the ТХІ level. Experimental group 1 consisted of a SC trauma, homotopic implantation of NeuroGelTM together with NSC of fetal (Е17) mice hippocampus (n=20); while group 2 ­ a SC trauma, homotopic implantation of NeuroGelTM (n=20); and group 3 ­ a SC trauma (n=16). Investigation of the function index and the spasticity index of posterior ipsilateral extremity was done in accordance to Basso-Beattie-Bresnahan and Ashworth scales. Association of the function index and the spasticity index of posterior ipsilateral extremity in all groups in various variants of the samples formation is ambiguous, witnessing possibility of additional correlation between these characteristics of a movement system. The NSC xenotransplantation in conjunction with NeuroGelTM changes the spasticity syndrome course, creates conditions for its facilitation in remote period after a SC trauma.

[[Durable persistence of a biocompatible foreign body in a vertebral channel in open penetrating trauma of a spinal cord: clinico-experimental and pathomorphological peculiarities].]

Simulation model of open penetrating wound of a spinal cord (SC) with its durable com- pression by biocompatible foreign body, was tasted. Experimental animals - mature male rats (inbred line, descendent from a Wistar breed); the trauma simulation model - a left- sided transsection of the SC half on the Txi level; experimental groups: the main (a SC trau- ma + homotopic implantation of microporous hydrogel fragment - foreign body [n=10]), groups of comparison (the SC trauma [n=16]; the SC trauma + homotopic implantation of chemically identical analogue of hydrogel - NeuroGelTM [n=20]). A SC compression by a foreign body worsens the regeneration process course essentially: during first 2 mo the function index of a hind ipsilateral extremity in experimental animals of the main group was the lowest in the experiment - (1.30 ? 0.94) points in accordance to BBB scale, during 3 - 4 mo - the function index had enhanced trustworthy - up to (2.35 ? 0.95) points in accor- dance to BBB scale, what is connected with lowering of a local pressure on a SC tissue due to change of the foreign body form and volume. In 24 weeks the function index of hind ipsi- lateral extremity had constituted (8.45 ? 0.92) points - while application of NeuroGeTM and (2.35 ? 0.95) points - of the foreign body; the tissue processes in the implants localization zone had differed essentially. The tasted simulation model reproduces satisfactory a mechanical component of the foreign body impact on a SC tissue. The SC compression reduction, even in a late follow-up period, had improved the conditions and results of recenerative process essentially.

[Role of neural stem cells in regeneration of the central nervous system].

Central nervous system (CNS) of adult mammalian and, in particular of people, is a typical example of organs that are not restored. However, the growing interest in the development of innovative treatments that are aimed at the regeneration damaged tissue CNS is based on the latest research in the field of stem cells and neurology. The recapitulation of normal neural development has become a vital strategy for CNS regeneration. Normal CNS development is initiated by the induction of stem cells in the CNS, i.e., neural stem cells (NSCs). Thus, the introduction or mobilization of NSCs could be expected to lead to CNS regeneration by recapitulating normal CNS development, in terms of the activation of the endogenous regenerative capacity and cell transplantation therapy. In this review we summarized the recent progress in study of basic stem cell biology, on the prospective identification of NSCs, the elucidation of the mechanisms of ontogenic changes, potential differentiation, and their therapeutic applications.