Intermittent hypoxia and stem cell implants preserve breathing capacity in a rodent model of amyotrophic lateral sclerosis.

Rationale: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease causing paralysis and death from respiratory failure. Strategies to preserve and/or restore respiratory function are critical for successful treatment. Although breathing capacity is maintained until late in disease progression in rodent models of familial ALS (SOD1(G93A) rats and mice), reduced numbers of phrenic motor neurons and decreased phrenic nerve activity are observed.

Gonadectomy and dehydroepiandrosterone (DHEA) do not modulate disease progression in the G93A mutant SOD1 rat model of amyotrophic lateral sclerosis.

Epidemiological studies have shown a higher incidence of amyotrophic lateral sclerosis (ALS) in men than women. Interestingly, there are clear gender differences in disease onset and progression in rodent models of familial ALS overexpressing mutated human superoxide dismutase-1 (SOD1-G93A). In the present study we sought to determine whether the alterations of serum steroid levels by gonadectomy or chronic treatment of neuroprotective neurosteroids can modulate disease onset and progression in a rat model of ALS (SOD1-G93A transgenic rats).

Acute glial activation by stab injuries does not lead to overt damage or motor neuron degeneration in the G93A mutant SOD1 rat model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where motor neurons within the brain and spinal cord are lost, leading to paralysis and death. Recently, a correlation between head trauma and the incidence of ALS has been reported. Furthermore, new invasive neurosurgical studies are being planned which involve inserting needles directly to the spinal cord.

Cervical spinal cord therapeutics delivery: preclinical safety validation of a stabilized microinjection platform.

Objective: The current series represents a preclinical safety validation study for direct parenchymal microinjection of cellular grafts into the ventral horn of the porcine cervical spinal cord.

Methods: Twenty-four 30- to 40-kg female Yorkshire farm pigs immunosuppressed with cyclosporine underwent a cervical laminectomy and ventral horn human neural progenitor cell injection. Cell transplantation in groups 1 to 3 (n = 6 pigs each) was undertaken with the intent of assessing the safety of varied injection volumes: 10, 25, and 50 microL injected at 1, 2.

Direct muscle delivery of GDNF with human mesenchymal stem cells improves motor neuron survival and function in a rat model of familial ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which there is a progressive loss of motor neurons and their connections to muscle, leading to paralysis. In order to maintain muscle connections in a rat model of familial ALS (FALS), we performed intramuscular transplantation with human mesenchymal stem cells (hMSCs) used as "Trojan horses" to deliver growth factors to the terminals of motor neurons and to the skeletal muscles. hMSCs engineered to secrete glial cell line-derived neurotrophic factor (hMSC-GDNF) were transplanted bilaterally into three muscle groups.

GDNF secreting human neural progenitor cells protect dying motor neurons, but not their projection to muscle, in a rat model of familial ALS.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease characterized by rapid loss of muscle control and eventual paralysis due to the death of large motor neurons in the brain and spinal cord. Growth factors such as glial cell line derived neurotrophic factor (GDNF) are known to protect motor neurons from damage in a range of models. However, penetrance through the blood brain barrier and delivery to the spinal cord remains a serious challenge.

Sexual dimorphism in disease onset and progression of a rat model of ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing the progressive loss of brain and spinal cord motor neurons. The exact etiology of ALS is still uncertain, but males have consistently been shown to be at a higher risk for the disease than females. Recently, transgenic rats overexpressing mutant forms of the human SOD1 (hSOD1) gene have been established as a valuable disease model of ALS.

GDNF delivery using human neural progenitor cells in a rat model of ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of spinal cord, brainstem, and cortical motor neurons. In a minority of patients, the disease is caused by mutations in the copper (2+)/zinc (2+) superoxide dismutase 1 (SOD1) gene. Recent evidence suggests that astrocytes are dysfunctional in ALS and may be a critical link in the support of motor neuron health.

Investigation into a role for the primitive streak in development of the murine allantois.

Despite its importance as the source of one of three major vascular systems in the mammalian conceptus, little is known about the murine allantois, which will become the umbilical cord of the chorio-allantoic placenta. During gastrulation, the allantois grows into the exocoelomic cavity as a mesodermal extension of the posterior primitive streak. On the basis of morphology, gene expression and/or function, three cell types have been identified in the allantois: an outer layer of mesothelial cells, whose distal portion will become transformed into chorio-adhesive cells, and endothelial cells within the core.

Multiple developmental roles of Ahnak are suggested by localization to sites of placentation and neural plate fusion in the mouse conceptus.

Ahnak is a gigantic (700 kD) phosphoprotein with a unique structure whose expression and cellular localization are dynamically regulated during cell cycle progression. Here, we report that Ahnak is localized to sites of major morphogenesis during mouse placentation and neurulation. Ahnak was found in: (i) derivatives of trophectoderm, including chorionic ectoderm prior to and during union with the ectoplacental cone, presumptive syncytiotrophoblast cells in the chorionic labyrinth, and giant cells at the trophoblast-uterine interface; (ii) the allantois prior to, during, and after union with the chorion; and (iii) the tips of the neural plate during formation of the neural tube.

Multiple developmental roles of Ahnak are suggested by localization to sites of placentation and neural plate fusion in the mouse conceptus.

Ahnak is a gigantic (700 kD) phosphoprotein with a unique structure whose expression and cellular localization are dynamically regulated during cell cycle progression. Here, we report that Ahnak is localized to sites of major morphogenesis during mouse placentation and neurulation. Ahnak was found in: (i) derivatives of trophectoderm, including chorionic ectoderm prior to and during union with the ectoplacental cone, presumptive syncytiotrophoblast cells in the chorionic labyrinth, and giant cells at the trophoblast-uterine interface; (ii) the allantois prior to, during, and after union with the chorion; and (iii) the tips of the neural plate during formation of the neural tube.