Enhancement of Dormant Pathways in the Brain following Rat Contusive Spinal Cord Injury

Spinal cord injury (SCI) induces distal effects on neural activity in the brain. To date, precise, high quality anatomical studies have not been performed. The goal of this study was to delineate neuroanatomical enhancement of dormant pathways in the brain following SCI using an appropriate serotype of an adeno-associated-virus (AAV) with a CAG promotor

DNA diagnosis in the NF2 gene

Neurofibromatosis 2 (NF2) is a genetic disorder characterized by the develop-ment of multiple tumors in the central nervous system. Recently, the NF2 gene has been cloned and found to encode a novel member of the protein 4.1 family which is thought to link integral membrane proteins to the cytoskeleton. The identification of the NF2 tumor suppresser gene has allowed us to screen for pathological mutations in the gene. We have studied germline mutations in the NF2 gene by direct sequence analysis of genomic DNA from blood samples of NF2 patients. In the present report, we demonstrate a novel pathological missense mutation in a patient with NF2, which reveals that the variant observed may affect important functional regions or alter the protein on a larger scale by affecting conformation or degradation

Mesenchymal Stem Cell Transplantation for Spinal Cord Injury: Current Status and Prospects

Since the 1990s, our group has been conducting basic research on regenerative medicine using various cell types to treat several central nervous system diseases, including spinal cord injury (SCI). We have reported many positive effects of the intravenous administration of mesenchymal stem cells (MSCs) derived from the bone marrow. In the current study, MSCs were administered intravenously to a rat model of severe SCI (crush injury) during the acute to subacute stages-considerable motor function recovery was observed. Furthermore, MSC transplantation in a chronic-phase SCI model improved motor function. In this review, we discuss recent updates in basic research on the intravenous infusion of MSCs and prospects for SCI research

Development of a middle cerebral artery occlusion model in the nonhuman primate and a safety study of i.v. infusion of human mesenchymal stem cells.

Most experimental stroke research is carried out in rodents, but given differences between rodents and human, nonhuman primate (NHP) models may provide a valuable tool to study therapeutic interventions. The authors developed a surgical method for transient occlusion of the M1 branch of middle cerebral artery (MCA) in the African green monkey to evaluate safety aspects of intravenous infusion of mesenchymal stem cells (hMSCs) derived from human bone marrow.The left Sylvian fissure was exposed by a small fronto-temporal craniotomy. The M1 branch of the MCA was exposed by microsurgical dissection and clipped for 2 to 4 hours. Neurological examinations and magnetic resonance imaging (MRI) were carried out at regular post-operative course. hMSCs were infused 1 hour after reperfusion (clip release) in the 3-hour occlusion model.During M1 occlusion, two patterns of changes were observed in the lateral hemisphere surface. One pattern (Pattern 1) was darkening of venous blood, small vessel collapse, and blood pooling with no venous return in cortical veins. Animals with these three features had severe and lasting hemiplegia and MRI demonstrated extensive MCA territory infarction. Animals in the second pattern (Pattern 2) displayed darkening of venous blood, small vessel collapse, and reduced but incompletely occluded venous flow and the functional deficit was much less severe and MRI indicated smaller infarction areas in brain. The severe group (Pattern 1) likely had less extensive collateral circulation than the less severe group (Pattern 2) where venous pooling of blood was not observed. The hMSC infused animals showed a trend for greater functional improvement that was not statistically significant in the acute phase and no additive negative effects.These results indicate inter-animal variability of collateral circulation after complete M1 occlusion and that hMSC infusion is safe in the developed NHP stroke model

Restoration of normal conduction properties in demyelinated spinal cord axons in the adult rat by transplantation of exogenous Schwann cells

Although remyelination of demyelinated CNS axons is known to occur after transplantation of exogenous glial cells, previous studies have not determined whether cell transplantation can restore the conduction properties of demyelinated axons in the adult CNS. To examine this issue, the dorsal columns of the adult rat spinal cord were demyelinated by x-irradiation and intraspinal injections of ethidium bromide. Cell suspensions of cultured astrocytes and Schwann cells derived from neonatal rats transfected with the (β-galactosidase) reporter gene were injected into the glial-free lesion site. After 3–4 weeks nearly all of the demyelinated axons were remyelinated by the transplanted Schwann cells. The dorsal columns were removed and maintained in an in vitro recording chamber; conduction properties were studied using field potential and intra-axonal recording techniques. The demyelinated axons exhibited conduction slowing and block, and a reduction in their ability to follow high-frequency stimulation. Axons remyelinated by transplantation of cultured Schwann cells exhibited restoration of conduction through the lesion, with reestablishment of normal conduction velocity. The axons remyelinated after transplantation showed enhanced impulse recovery to paired-pulse stimulation and greater frequency-following capability as compared with both demyelinated and control axons. These results demonstrate the functional repair of demyelinated axons in the adult CNS by transplantation of cultured myelin-forming cells from the peripheral nervous system in combination with astrocytes