A Preliminary Study of Intravenous Surfactants in Paraplegic Dogs: Polymer Therapy in Canine Clinical SCI

Abstract

Hydrophilic polymers, both surfactants and triblock polymers, are known to seal defects in cell membranes. In previous experiments using laboratory animals, we have exploited this capability using polyethylene glycol (PEG) to repair spinal axons after severe, standardized spinal cord injury (SCI) in guinea pigs. Similar studies were conducted using a related co-polymer Poloxamer 188 (P 188). Here we carried out initial investigations of an intravenous application of PEG or P 188 (3500 Daltons, 30% w/w in saline; 2 mL/kg I.V. and 2 mL/kg body weight or 300 mL P 188 per kg, respectively) to neurologically complete cases of paraplegia in dogs. Our aim was to first determine if this is a clinically safe procedure in cases of severe naturally occurring SCI in dogs. Secondarily, we wanted to obtain preliminary evidence if this therapy could be of clinical benefit when compared to a larger number of similar, but historical, control cases. Strict entry criteria permitted recruitment of only neurologically complete paraplegic dogs into this study. Animals were treated by a combination of conventional and experimental techniques within approximately 72 h of admission for spinal trauma secondary to acute, explosive disk herniation. Outcome measures consisted of measurements of voluntary ambulation, deep and superficial pain perception, conscious proprioception in hindlimbs, and evoked potentials (somatosensory evoked potentials [SSEP]). We determined that polymer injection is a safe adjunct to the conventional management of severe neurological injury in dogs. We did not observe any unacceptable clinical response to polymer injection; there were no deaths, nor any other problem arising from, or associated with, the procedures. Outcome measures over the 6-8-week trial were improved by polymer injection when compared to historical cases. This recovery was unexpectedly rapid compared to these comparator groups. The results of this pilot trial provides evidence consistent with the notion that the injection of inorganic polymers in acute neurotrauma may be a simple and useful intervention during the acute phase of the injury.

A simplified method of walking track analysis to assess short-term locomotor recovery after acute spinal cord injury caused by thoracolumbar intervertebral disc extrusion in dogs

“…The high incidence of spontaneous SCI in dogs makes them an important animal model for human SCI (Rice et al, 2009). Dogs offer a genetically similar, but environmentally heterogeneous study population, with comparable mechanisms of injury and resultant pathology to that in humans, which can bridge the gap between experimental rodent models and the human SCI population (Borgens et al, 1999; Laverty et al, 2004; Olby et al, 2004; Jeffery et al, 2006). Successful clinical trials in dogs with spontaneous SCI may lead to the development of interventional therapies that can help both dogs and humans.…”

Protective effects of high-molecular weight Polyethylene Glycol (PEG) in human lung endothelial cell barrier regulation: Role of actin cytoskeletal rearrangement

“…Furthermore, we recently utilized PEG to act as a surrogate mucin lining by providing protection against bacterial infections on intestinal epithelial cells in a murine model of lethal gut-derived sepsis (Wu et al, 2004). However, the most compelling use of PEG has been in the repair of severed neurons with rapid fusion of severed spinal cord nerve fibers following PEG treatment (Borgens and Shi, 2000; Shi and Borgens, 1999; Shi and Borgens, 2000; Shi et al, 1999) and for successful repair of guinea pig (Borgens and Bohnert, 2001) and canine (Laverty et al, 2004) spinal cord injuries. The mechanism of PEG-induced neuroprotection involves direct interaction of PEG with the mitochondria (Luo et al, 2004) and inhibiting free radical production after acute spinal cord injury (Luo et al, 2002).…”

Hydrogels and Cell Based Therapies in Spinal Cord Injury Regeneration

“…This was followed by a significant recovery of the cutaneous trunci muscle (CTM) reflex, which is a good index of white matter integrity [212]. In another study, using dogs as an animal model of SCI, PEG injection in the acute phase was shown as clinically safe and induced a rapid recovery in different outcome measures, as compared to conventionally treated dogs [213]. Also, coupling PEG hydrogels with NT-3 and implanting these in a rat model of SCI provided improved locomotor behavior to lesioned animals and greater axonal growth, in comparison to controls treated with hydrogel alone [214].…”