Polyethylene glycol repairs membrane damage and enhances functional recovery: a tissue engineering approach to spinal cord injury

Shi, Riyi

doi:10.1007/s12264-013-1364-5

Cited by 59 publications

(50 citation statements)

References 62 publications

(92 reference statements)

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“…It is a surfactant used in cell culture for its ability to fuse cell membranes . After acute spinal cord injury, membrane permeability is disrupted with devastating results, and this membrane disruption as well as damaged intracellular organelles present a therapeutic target for PEG . Experimental work in an ex vivo spinal cord preparation demonstrated restoration of conduction across crushed spinal cord .…”

Section: Discussionmentioning

confidence: 99%

“…However, the results of these trials are controversial, and MPSS has not been adopted as a standard of care in human medicine . Polyethyelene glycol has received attention for its ability to fuse membranes and has improved outcome in experimental models of spinal cord injury . It also has been evaluated in a clinical trial in dogs with the most severe grade of injury caused by IVDH .…”

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confidence: 99%

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A Placebo‐Controlled, Prospective, Randomized Clinical Trial of Polyethylene Glycol and Methylprednisolone Sodium Succinate in Dogs with Intervertebral Disk Herniation

Olby

Muguet-Chanoit

Lim

et al. 2015

Veterinary Internal Medicne

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BackgroundAcute intervertebral disk herniation (IVDH) is a common cause of spinal cord injury in dogs and currently there is no proven medical treatment to counter secondary injury effects. Use of methylprednisolone sodium succinate (MPSS) or polyethylene glycol (PEG) as neuroprotectants is advocated but controversial because neither treatment has been tested in placebo‐controlled, randomized, blinded trials in dogs.HypothesisPolyethylene glycol will improve the outcome of severe spinal cord injury caused by IVDH compared to MPSS or placebo.AnimalsClient‐owned dogs with acute onset of thoracolumbar IVDH causing paralysis and loss of nociception for <24 hours.MethodsDogs were randomized to receive MPSS, PEG, or placebo; drugs appeared identical and group allocation was masked. Drug administration was initiated once the diagnosis of IVDH was confirmed and all dogs underwent hemilaminectomy. Neurologic function was assessed 2, 4, 8, and 12 weeks postoperatively using an open field gait score (OFS) as the primary outcome measure. Outcomes were compared by the Wilcoxon rank sum test.ResultsSixty‐three dogs were recruited and 47.6% recovered ambulation. 17.5% developed progressive myelomalacia but there was no association with group. There was no difference in OFS among groups. Although full study power was not reached, conditional power analyses indicated the futility of continued case recruitment.ConclusionsThis clinical trial did not show a benefit of either MPSS or PEG in the treatment of acute, severe thoracolumbar IVDH when used as adjunctive medical treatment administered to dogs presenting within 24 hours of onset of paralysis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A Placebo‐Controlled, Prospective, Randomized Clinical Trial of Polyethylene Glycol and Methylprednisolone Sodium Succinate in Dogs with Intervertebral Disk Herniation

Olby

Muguet-Chanoit

Lim

et al. 2015

Veterinary Internal Medicne

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“…James Fawcett of the University of Cambridge [18] summarizes work centered around combinatorial treatment with Chondrotinase ABC and other approaches to achieve regeneration based on progress in molecular signaling in glial scar inhibition. Riyi Shi of Purdue University [19] discusses an interesting tissueengineering approach using polyethylene glycol, which reseals membrane and repairs mitochondria to reduce oxidative stress and minimize secondary injury. Agnes…”

Section: Injury Can Cause Neuronal Loss So Keeping Neurons Alive Is mentioning

confidence: 99%

An update on spinal cord injury research

Zou

2013

Neurosci. Bull.

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Spinal cord injury (SCI) is an ever-increasing challenge.Severe injury can cause long-term loss of sensory and motor functions, as well as other chronic conditions, such as neuropathic pain and autonomic dysreflexia. So far, most research has been focused on acute injury. However, due to the lack of treatment, more and more individuals with this condition enter a chronic state, to which very little research effort has been dedicated. SCI is a complex condition. It involves damage to axons, death of neurons, neuroinflammation, glial scar formation, loss of myelin, and lack of remyelination. It is clear that effective treatment will require combinatorial approaches. The 12 invited articles for this special issue on SCI provide an update on many of these areas of SCI research. Here, I highlight the articles and reviews by theme.Severe SCI involves severing of axons, breaking ascending and descending connections. Inhibitory molecules in the environment of the adult central nervous system, such as the myelin-associated inhibitors and proteoglycans in glial scars, were thought to be the major cause of the lack of regeneration for many years [1] .However, efforts to regenerate axons across a lesion site in the mammalian spinal cord by overcoming this inhibition have not been successful. In some cases, axon regeneration into cell grafts can be achieved, as in studies using preconditioning lesion paradigms of sensory axons [2] .But few axons project beyond the lesion and reach longrange targets. In recent years, more attention has been shifted to enhancing the intrinsic growth capacity of adult central nervous system axons. Deletion of pTEN (phosphatase and tensin homolog) induces unprecedented regeneration across the fully-transacted spinal cord [3] .Neurons derived from embryos or induced pluripotent stem cells that have strong intrinsic growth properties can ignore inhibitory cues in the adult spinal cord and grow long distances up and down the cord [4] . In partial injury, rerouting and sprouting of axons result in circuit reorganization in the spared tissue and have been shown to be effective in restoring function using a combination of pharmacological and electrophysiological stimulation and robot-assisted rehabilitation techniques [5,6] . Molecular mechanisms that promote or inhibit axon growth have been studied, using various injury paradigms, in different neuronal types and species. Some species have poor central regeneration, whereas others have the capacity to regenerate. Axons in the peripheral nervous system of mammals also show extensive regeneration. The review by Martin Oudega of the University of Pittsburgh [7] provides a comprehensive discussion comparing the molecular mechanisms found in mammals and zebrafish.These comparisons allow for a better understanding of the underlying principles. Remarkably, regeneration in the zebrafish central nervous system is also incomplete. Some axon tracts can regenerate but others cannot. This makes zebrafish an interesting model system for SCI research along with the ...

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“…18. № 3 structural properties of cell membranes [21]. In addition, low molecular PEG are actively involved in molecular mechanisms of recovery of plasma membranes of cells and preventing damage to mitochondria [22].…”

Section: Discussionmentioning

confidence: 99%

Optimization of human somatic cells cryopreservation protocols by polyethylene glycols

Perepelytsina¹,

Ugnivenko²,

Burlaka³

et al. 2016

MCCh

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Polyethylene glycol repairs membrane damage and enhances functional recovery: a tissue engineering approach to spinal cord injury

Cited by 59 publications

References 62 publications

A Placebo‐Controlled, Prospective, Randomized Clinical Trial of Polyethylene Glycol and Methylprednisolone Sodium Succinate in Dogs with Intervertebral Disk Herniation

A Placebo‐Controlled, Prospective, Randomized Clinical Trial of Polyethylene Glycol and Methylprednisolone Sodium Succinate in Dogs with Intervertebral Disk Herniation

An update on spinal cord injury research

Optimization of human somatic cells cryopreservation protocols by polyethylene glycols

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