[Show abstract][Hide abstract] ABSTRACT: Traumatic brain injuries and degenerative neurological disorders such as Alzheimer's dementia, Parkinson's disease, amyotrophic lateral sclerosis and many others are characterized by loss of brain cells and supporting structures. Restoring microanatomy and function using stem cells is a promising therapeutic approach. Among the many various sources, adipose-derived stem cells (ADSCs) are one of the most easily harvested alternatives, they multiply rapidly, and they demonstrate low immunogenicity with an ability to differentiate into several cell types. The objective of this study was to evaluate the effect of xenotransplanted human ADSCs on post-traumatic regeneration of rat sciatic nerve. Peripheral reconstruction following complete sciatic transection and autonerve grafting was complemented by intra-operative injection of hADSCs into the proximal and distal stumps. The injury caused gliosis and apoptosis of sensory neurons in the lumbar 5 (L5) ganglia in the control rodents; however, animals treated with hADSCs demonstrated a smaller amount of cellular loss. Formation of amputation neuroma, which hinders axonal repair, was less prominent in the experimental group, and immunohistochemical analysis of myelin basic protein showed good myelination 65 days after surgery. At this point, control groups still exhibited high levels of microglia/macrophage-specific marker Iba-1 and proliferating cell nuclear antigen, the mark of an ongoing inflammation and incomplete axonal growth 2 months after the injury. This report demonstrates that hADSCs promote neuronal survival in the spinal ganglion, fuel axonal repair and stimulate the regeneration of peripheral nerves.
Clinical and Experimental Medicine 06/2015; DOI:10.1007/s10238-015-0364-3 · 2.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In experiments on rats with lateral TVIII hemisection of the spinal cord and transplantation of ensheating olfactory cells, we studied structural changes at the lesion site and adjacent rostral and dorsal regions of the spinal cord. The state of oligodendrocytes and myelin fibers and motor function in experimental animal were analyzed. Open field testing (BBB test) showed that motor functions steadily increased (by 13% on average) within the interval from day 21 to day 53 after transplantation. Histological examination showed that groups of transplanted cells carrying human nuclear marker (HNu(+)cells) were still present at the lesion site 30 days after surgery. Some of these cells migrated in the rostral and caudal directions from the injection site to a distance up to 6 mm. At the initial period after hemisection, the number of oligodendrocytes (O4(+)-cells) in the immediate vicinity to the lesion site decreased 2-fold, but no significant changes in the number of neurons were found in the rostral and dorsal fragments of the spinal cord compared to the corresponding parameter in controls. Sixty days after transplantation, the cross-section area in the rostral part of the spinal cord at a distance of 3 mm from damage site increased by 15.3% compared to the control. The number of O4(+)-cells at the lesion site and in adjacent rostral and caudal parts of the spinal cord by 22.8% surpassed that in the control group. The number of remyelinated axons also increased. These findings suggest that the absence of pronounced structural changes in the rostral and caudal parts of the spinal cord compared to lesion site at early stages after damage and cell transplantation. At the same time, pronounced activation of oligodendrocytes in this region suggests their involvement together with Schwann cells into remyelination of regenerating axons, which can serve as a factor of partial restoration of motor functions after spinal cord injury.
Bulletin of Experimental Biology and Medicine 07/2010; 149(1):135-9. DOI:10.1007/s10517-010-0892-5 · 0.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Allotransplantation of the liver, hindlimb, and bone marrow tissues from 14-day-old embryos into the sciatic nerve had a modulatory effect on survival of various populations of axotomized neurons in L5 spinal ganglion in an adult rat.
Bulletin of Experimental Biology and Medicine 05/2009; 147(4):537-8. DOI:10.1007/s10517-009-0540-0 · 0.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 1. The possibility of a neuro-protective effect of Xymedon as a pharmacological stimulator of nerve regeneration has been studied through Schwann cells (SCs) located in the potential area of regenerating nerve fibers' growth. 2. Xymedon was injected into the silicone chamber connecting the central and peripheral stumps of the rat's sciatic nerve. Carboxymethyl cellulose was used as a depositioned medium. 3. A 0.95% concentration of Xymedon increased the sciatic nerve functional index (SFI) values on the 14th, 21st and 28th day after the operation. By day 30, the total number of survival neurons in the L5 dorsal root ganglion (DRG) on the ipsilateral side increased with the following changes in Xymedon concentration: [see text] The number of surviving sensory neurons in the group with 0.95% Xymedon increased by 36% (p < 0.05) compared with animals with depositioned medium but Xymedon free. 4. It is suggested that the positive effects of Xymedon on neural regeneration and recovery of motor function support the potential use of Xymedon for the treatment of peripheral nerve injuries.
[Show abstract][Hide abstract] ABSTRACT: Trauma to the peripheral processes of sensory neurons of different subpopulations was followed by indirect immunohistochemical analysis of the expression of Bcl-X(L) and Bax, which are, respectively, antiapoptotic and proapoptotic proteins of the Bcl-2 family, and also of the cytokine interleukin-1beta, with the aim of identifying the roles of these substances in controlling apoptosis. The survival abilities of these neurons after central and peripheral axotomy were compared by studying the expression of the high molecular weight component of the neurofilament triplet NF200 and isolectin B4 (IB4). By day 30 after central axotomy, there were no changes in the total numbers of neurons in ganglia L(IV)-L(V) in rats, though there were significant reductions in the numbers of NF200+ neurons. In spinal ganglion L(V) of mice, the proapoptotic protein was detected in the nuclei of 46% of small neurons, which account for 20% of all neurons in the ganglion. By day 30 after nerve compression, Bax was expressed in the nuclei of 30% of neurons and the cytoplasm of 20% of neurons. In intact animals, the antiapoptotic protein Bcl-X(L) was seen in the cytoplasm of 30% of small neurons, as well as in satellite cells surrounding large and intermediate neurons. By day 30 after nerve trauma, Bcl-X(L) was not expressed in spinal ganglion L(V). Interleukin-1beta was present in the cytoplasm of 17% of neurons belonging to the subpopulations of large and intermediate neurons. By day 30 after nerve compression, interleukin-1 beta+ neurons were not identified.
Neuroscience and Behavioral Physiology 07/2005; 35(5):457-60. DOI:10.1007/s11055-005-0078-1
[Show abstract][Hide abstract] ABSTRACT: Using indirect inmunohistochemical method, the expression of Bcl-XL and Bax, anti- and proapoptotic proteins of Bcl-2 family, as well as of cytokine IL-1beta were studied to demonstrate the role of these substances in apoptosis regulation of sensory neurons of different subpopulations after the severance of their peripheral processes. For comparison of the capacity of these neurons to survive after central and peripheral axotomy, the expression of high-molecular component of neurofilament triplet NF200 and isolectin B4 (IB4) binding were studied. At day 30 after central axotomy, the total number of neurons in LIV-LV ganglia of rat was not changed, but the number of NF200+ neurons was decreased. In mouse Lv dorsal root, proapoptotic BaX protein was demonstrated in the nuclei of 46% of small neurons that accounts for 20% of the total neuronal number in this ganglion. By day 30 after the nerve crush separate Bax expression was found in the nuclei of 30% and in the cytoplasm of 20% of neurons. In intact animals, dorsal root ganglion antiapoptotic Bcl-XL protein was expressed in the cytoplasm of 30% of small neurons, as well as in satellite cells surrounding large and intermediate neurons. At day 30 after the nerve crush Bcl-XL expression in LV ganglion was not detected. IL-1beta was present in the cytoplasm of 17% of neurons belonging predominantly to the subpopulations of large and intermediate neurons. By day 30 after the nerve crush IL-1(+-neurons were not found.