Neurobiology of disease
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Neurobiology of disease · May 2007
Human adult olfactory neural progenitors promote axotomized rubrospinal tract axonal reinnervation and locomotor recovery.
We investigated the effects of engrafted human adult olfactory neuroepithelial neurosphere forming cells (NSFCs) on regeneration and reinnervation of rubrospinal tract (RST) axons and locomotor recovery following partial cervical hemisection that completely ablated the RST. Weekly behavioral testing showed greater functional recovery of forelimb use during the 12 weeks after NSFCs engraftment than in the control rats. ⋯ Further study of forelimb functional recovery in NSFCs-engrafted subgroups considered the effects of a second dorsolateral funiculotomy, irreversibly destroying the recovery, and the injection of muscimol, blocking RST neuronal activity reversibly. These results highlight the unique potential of human olfactory neuroepithelial-derived progenitors as an autologous cell source for spinal cord repair.
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Neurobiology of disease · May 2007
Inhibition of p38 mitogen activated protein kinase activation and mutant SOD1(G93A)-induced motor neuron death.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the selective loss of motor neurons. Stress activated protein kinases (SAPK) have been suggested to play a role in the pathogenesis of ALS. We studied the relevance of p38 MAPK for motor neuron degeneration in the mutant SOD1 mouse. ⋯ Semapimod, a p38 MAPK inhibitor suitable for clinical use, prolonged survival of mutant SOD1 mice to a limited extent, but largely protected motor neurons and proximal axons from mutant SOD1-induced degeneration. Our data confirm the abnormal activation of p38 MAPK in mutant SOD1 mice and the involvement of p38 MAPK in mutant SOD1-induced motor neuron death. We demonstrate the effect of p38 MAPK inhibition on survival of mutant SOD1 mice and reveal a dissociation between the effect on survival of motor neurons and that on survival of the animal, the latter likely depending on the integrity of the entire motor axon.