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

The integrity of the neuronal membrane is crucial for its function and cellular survival; thus, ineffective repair of damaged membranes may be one of the key elements underlying the neuronal degeneration and overall functional loss that occurs after spinal cord injury （SCI）. It has been shown that polyethylene glycol （PEG） can reseal axonal membranes following various injuries in multiple in vitro and in vivo injury models. In addition, PEG may also directly prevent the effects of mitochondria-derived oxidative stress on intracellular components. Thus, PEG repairs mechanically injured cells by at least two distinct pathways： resealing of the disrupted plasma membrane and direct protection of mitochondria. Besides repairing primary membrane damage, PEG treatment also results in significant attenuation of oxidative stress, likely due to its capacity to reseal the membrane, thereby breaking the cycle of cellular damage and free-radical production. Based on this, in addition to the practicality of its application, we expect that PEG may be established as an effective treatment for SCI where membrane disruption and mitochondriai damage are implicated.

Mechanisms of neuronal membrane sealing following mechanical trauma

Membrane integrity is crucial for maintaining the intricate signaling and chemically-isolated intracellular environment of neurons; disruption risks deleterious effects, such as unregulated ionic flux, neuronal apoptosis, and oxidative radical damage as observed in spinal cord injury and traumatic brain injury. This paper, in addition to a discussion of the current understanding of cellular tactics to seal membranes, describes two major factors involved in membrane repair. These are line tension, the hydrophobic attractive force between two lipid free-edges, and membrane tension, the rigidity of the lipid bilayer with respect to the tethered cortical cytoskeleton. Ca2~, a major mechanistic trigger for repair processes, increases following flux through a membrane injury site, and activates phospholipase enzymes, calpain-mediated cortical cytoskeletal proteolysis, protein kinase cascades, and lipid bilayer microdomain modification. The membrane tension appears to be largely modulated through vesicle dynamics, cytoskeletal organization, membrane curvature, and phospholipase manipulation. Dehydration of the phospholipid gap edge and modification of membrane packaging, as in temperature variation, experimentally impact line tension. Due to the time-sensitive nature of axonal sealing, increasing the efficacy of axolemmal sealing through therapeutic modification would be of great clinical value, to deter secondary neurodegenerative effects. Better therapeutic enhancement of membrane sealing requires a complete understanding of its intricate underlying neuronal mechanism.