ABSTRACT
Peripheral nerve grafts have shown the ability to facilitate central axonal growth and regenerate the adult central nervous system. However, the detailed description of a technique for atraumatic graft placement within the brain is lacking. We present a stereotactic procedure to implant a peripheral nerve graft within a rat's brain with minimal brain tissue damage. The procedure permits a correct graft placement joining two chosen points, and the survival and integration of the graft in the host tissue with a light glial reaction, with evidence of central axonal growth inside the graft, at least up to 8 weeks after its implantation.
Subject(s)
Brain/surgery , Nerve Regeneration/physiology , Sciatic Nerve/transplantation , Stereotaxic Techniques , Animals , Brain/ultrastructure , Microscopy, Electron, Transmission , RatsABSTRACT
Degenerative spinal motor diseases, like amyotrophic lateral sclerosis, are produced by progressive degeneration of motoneurons. Their clinical manifestations include a progressive muscular weakness and atrophy, which lead to paralysis and premature death. Current pharmacological therapies fail to stop the progression of motor deficits or to restore motor function. The purpose of our study was to explore the possible beneficial effect of mouse adult hematopoietic stem cells (hSCs) transplanted into the spinal cord of a mouse model of motoneuron degeneration. Our results show that grafted hSCs survive in the spinal cord. In addition, the number of motoneurons in the transplanted spinal cord is larger than in non-transplanted mdf mice at the same spinal cord segments and importantly, motor function significantly improves. These effects can be explained by the increased levels of glial cell line derived neurotrophic factor (GDNF) around host motoneurons produced by the grafted cells. Thus, these experiments demonstrate the neuroprotective effect of adult hSCs in the model employed and indicate that this cell type may contribute to ameliorating motor function in degenerative spinal motor diseases.
Subject(s)
Cell Differentiation/physiology , Graft Survival/physiology , Hematopoietic Stem Cells/metabolism , Motor Neuron Disease/therapy , Spinal Cord/surgery , Stem Cell Transplantation/methods , Action Potentials/physiology , Animals , Cell Count , Cell Lineage/physiology , Cytoprotection/physiology , Disease Models, Animal , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Mice , Mice, Neurologic Mutants , Motor Neuron Disease/metabolism , Motor Neuron Disease/physiopathology , Motor Neurons/physiology , Muscle, Skeletal/innervation , Muscle, Skeletal/physiology , Recovery of Function/physiology , Spinal Cord/physiopathologyABSTRACT
Adult stem cells may be an invaluable source of plastic cells for tissue regeneration. The bone marrow contains different subpopulations of adult stem cells easily accessible for transplantation. However the therapeutic value of adult stem cell is a question of debate in the scientific community. We have investigated the potential benefits of adult hematopoietic stem cell transplantation in animal models of demyelinating and motor neuron diseases. Our results suggest that transplantation of HSC have direct and indirect neuroregenerative and neuroprotective effects.
Subject(s)
Hematopoietic Stem Cell Transplantation/trends , Nervous System Diseases/therapy , Animals , Demyelinating Diseases/therapy , Humans , Mice , Motor Neuron Disease/therapy , Nerve Regeneration , Neurodegenerative Diseases/therapyABSTRACT
Intracellular recordings from neurons in the mouse trigeminal ganglion (TG) in vitro were used to characterize changes in membrane properties that take place from early postnatal stages (P0-P7) to adulthood (>P21). All neonatal TG neurons had uniformly slow conduction velocities, whereas adult neurons could be separated according to their conduction velocity into Adelta and C neurons. Based on the presence or absence of a marked inflection or hump in the repolarization phase of the action potential (AP), neonatal neurons were divided into S- (slow) and F-type (fast) neurons. Their passive and subthreshold properties (resting membrane potential, input resistance, membrane capacitance, and inward rectification) were nearly identical, but they showed marked differences in AP amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and afterhyperpolarization (AHP) duration. Adult TG neurons also segregated into S- and F-type groups. Differences in their mean AP amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and AHP duration were also prominent. In addition, axons of 90% of F-type neurons and 60% of S-type neurons became faster conducting in their central and peripheral branch, suggestive of axonal myelination. The proportion of S- and F-type neurons did not vary during postnatal development, suggesting that these phenotypes were established early in development. Membrane properties of both types of TG neurons evolved differently during postnatal development. The nature of many of these changes was linked to the process of myelination. Thus myelination was accompanied by a decrease in AP duration, input resistance (R(in)), and increase in membrane capacitance (C). These properties remained constant in unmyelinated neurons (both F- and S-type). In adult TG, all F-type neurons with inward rectification were also fast-conducting Adelta, suggesting that those F-type neurons showing inward rectification at birth will evolve to F-type Adelta neurons with age. The percentage of F-type neurons showing inward rectification also increased with age. Both F- and S-type neurons displayed changes in the sensitivity of the AP to reductions in extracellular Ca(2+) or substitution with Co(2+) during the process of maturation.
