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Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary(More)
Astrocytes in the CNS respond to tissue damage by becoming reactive. They migrate, undergo hypertrophy, and form a glial scar that inhibits axon regeneration. Therefore, limiting astrocytic responses represents a potential therapeutic strategy to improve functional recovery. It was recently shown that the epidermal growth factor (EGF) receptor is(More)
Amyotrophic lateral sclerosis (ALS), spinal bulbar muscular atrophy (or Kennedy's disease), spinal muscular atrophy and spinal muscular atrophy with respiratory distress 1 are neurodegenerative disorders mainly affecting motor neurons and which currently lack effective therapies. Recent studies in animal models as well as primary and embryonic stem cell(More)
BACKGROUND Prostaglandins, synthesized in the spinal cord in response to noxious stimuli, are known to facilitate nociceptive transmission, raising questions about their role in neuropathic pain. The current study tested the hypothesis that spinal nerve ligation-induced allodynia is composed of an early prostaglandin-dependent phase, the disruption of which(More)
Using a rat model of ischemic paraplegia, we examined the expression of spinal AMPA receptors and their role in mediating spasticity and rigidity. Spinal ischemia was induced by transient occlusion of the descending aorta combined with systemic hypotension. Spasticity/rigidity were identified by simultaneous measurements of peripheral muscle resistance(More)
To determine if spinal prostaglandins (PG) contribute to tactile allodynia, male, Sprague-Dawley rats were fitted with either intrathecal (i.t.) microdialysis or drug delivery catheters 3 days before tight ligation of the left lumber 5/6 spinal nerves. Paw withdrawal thresholds (PWT) were determined using von Frey filaments. Ligated rats developed tactile(More)
BACKGROUND Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1) causes an inherited form of Amyotrophic Lateral Sclerosis (ALS). Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs) into the(More)
Tactile allodynia can be modeled in experimental animals by acutely blocking spinal glycine or GABA(A) receptors with intrathecal (i.t.) strychnine (STR) or bicuculline (BIC), respectively. To test the hypothesis that glycine and GABA effect cooperative (supra-additive) inhibition of touch-evoked responses in the spinal cord, male Sprague-Dawley rats,(More)
In recent studies using a rat aortic balloon occlusion model, we have demonstrated that spinal grafting of rat or human neuronal precursors or human postmitotic hNT neurons leads to progressive amelioration of spasticity and rigidity and corresponding improvement in ambulatory function. In the present study, we characterized the optimal dosing regimen and(More)
In experimental and clinical studies, an objective assessment of peripheral muscle resistance represents one of the key elements in determining the efficacy of therapeutic manipulations (e.g. pharmacological, surgical) aimed to ameliorate clinical signs of spasticity and/or rigidity. In the present study, we characterize a newly developed limb flexion(More)