Advances in molecular therapies for targeting pathophysiology in spinal cord injury.

INTRODUCTION: Spinal cord injury (SCI) affects 25,000-50,000 people around the world each year and there is no cure for SCI patients currently. The primary injury damages spinal cord tissues and secondary injury mechanisms, including ischemia, apoptosis, inflammation, and astrogliosis, further exacerbate the lesions to the spinal cord. Recently, researchers have designed various therapeutic approaches for SCI by targeting its major cellular or molecular pathophysiology. AREAS COVERED: Some strategies have shown promise in repairing injured spinal cord for functional recoveries, such as administering neuroprotective reagents, targeting specific genes to promote robust axon regeneration of disconnected spinal fiber tracts, targeting epigenetic factors to enhance cell survival and neural repair, and facilitating neuronal relay pathways and neuroplasticity for restoration of function after SCI. This review focuses on the major advances in preclinical molecular therapies for SCI reported in recent years. EXPERT OPINION: Recent progress in developing novel and effective repairing strategies for SCI is encouraging, but many challenges remain for future design of effective treatments, including developing highly effective neuroprotectants for early interventions, stimulating robust neuronal regeneration with functional synaptic reconnections among disconnected neurons, maximizing the recovery of lost neural functions with combination strategies, and translating the most promising therapies into human use.

A model for the collective synchronization of flashing in Photinus carolinus.

Recent empirical investigations have characterized the synchronized flashing behaviours of male Photinus carolinus fireflies in their natural habitat in Great Smoky Mountain National Park as well as in controlled environments. We develop a model for the flash dynamics of an individual firefly based on a canonical elliptic burster, a slow-fast dynamical system that produces a repeating pattern of multiple flashes followed by a quiescent period. We show that a small amount of noise renders that oscillation very irregular, but when multiple model fireflies interact through their flashes, the behaviour becomes much more periodic. We show that the aggregate behaviour is qualitatively similar to the experimental findings. We next distribute the fireflies in a two-dimensional spatial domain and vary the interaction range. In addition to synchronization, various spatio-temporal patterns involving propagation of activity emerge spontaneously. Finally, we allow a certain number of fireflies to move and demonstrate how their speed affects the rate and degree of synchronization.