Reconstruction of the spinal cord of spinal transected dogs with polyethylene glycol

Abstract

Background: Our study shows that a membrane sealant/fiber fusogen polyethylene glycol (PEG) applied immediately on a sharp section of the spinal cord can mend the cord and lead to exceptional levels of motor recovery, with some animals almost normal.

Materials and methods: Before deploying such technology in man, long-term data in large mammals that exclude delayed complications (e.g., central pain), confirm the stability of motor recovery, and provide histological evidence of fiber regrowth are necessary. Here, we provide such evidence in dogs followed up over 6 months and in 2 cases up to 1 year along with imaging and histologic data.

Results: We show that dogs whose dorsal cord has been fully transected recover locomotion after immediate treatment with a fusogen (PEG). No pain syndrome ensued over the long term. Diffusion tensor imaging magnetic resonance and histological, including immunohistochemical, data confirmed the re-establishment of anatomical continuity along with interfacial axonal sprouting.

Conclusions: This study proves that a form of irreversible spinal cord injury (SCI) can effectively be treated and points out a way to treat SCI patients.

Keywords: Polyethylene glycol; spinal cord fusion; spinal cord injury.

Figure 1:

Representative diffusion tensor imaging scan after polyethylene glycol treatment (B and C) and placebo (A) at 6 months. The sectional gap in controls – unlike treatment animals – is still visible (A, arrow).

Figure 2:

Histology and immunohistochemistry. Controls: a1: hematoxylin-eosin (HE) sagittal view of the cord: notice poor take-up of the stain by interface tissues. a2: chromotropic acid 2R-Brilliant Green (C-2R-G) staining of an axial slice showing widespread Wallerian degeneration. a3: C-2R-G stained sections above, at and below injury level: notice absence of axons across the interface. a4: neurofilament 200 (NF200) DAPI and 5HT DAPI sections. Notice near absence of regrowing fibers across the interface. Polyethylene glycol: b1: HE sagittal view of the cord: notice bright coloring as stains are taken up by treated tissues. b2: C-2R-G staining of an axial slice showing widely conserved axons at the interface (arrows). b3: C-2R-G stained sections above and below injury level: notice the abundance of axons across the interface. b4: NF200 DAPI and 5HT DAPI sections. Notice regrowing fibers across the interface.

Figure 3:

(a-c) Block statistics of histology assessment (GraphPad): notice the neuroprotective effects of polyethylene glycol as cavitation is largely avoided and axons spared. No effects on scarring were noticed.