Nanomedicine and chemical imaging approaches for traumatic spinal cord injury

Traumatic spinal cord injury (SCI) results in immediate disruption of cell membranes in affected neural and endothelial tissues, followed by extensive secondary neurodegenerative processes. Due to the complication of the neurodegenerative processes, currently there is no golden therapy for SCI. Our strategy is to seal the damaged membranes at the early stage of SCI. Here we show that axonal membranes injured by compression can be effectively repaired by using self-assembled monomethoxy poly(ethylene glycol)-poly(D,L-lactic acid) di-block copolymer micelles (60 nm diameter). Injured spinal tissue incubated with micelles showed rapid restoration of compound action potential and reduced calcium influx into axons. Intravenously injected micelles effectively recovered the locomotor function. The micelles showed no adverse effects after systemic administration to live rats.

On the other hand, we have employed nonlinear optical microscopy to study tissue pathophysiology following SCI. The integration of different imaging modalities such as two-photon excited fluorescence (TPEF), sum frequency generation (SFG), and coherent anti-Stokes Raman scattering (CARS) on the sample platform enabled our investigation of acrolein induced demyelination through nodes of Ranvier. By employing inherent CARS signal from myelin sheath and strategies to minimize surgery, motion distortion and scar formation, we demonstrated high resolution in vivo imaging of normal and injured spinal cord in live rats. Longitudinal visualization of de- and re-myelination at single axon level provides a novel platform for rational design of therapies aimed at promoting myelin plasticity and repair.