The Effect of Poloxamer-188 on Neuronal Cell Recovery from Mechanical Injury

Abstract

Neuronal injury resulting from mechanical deformation is poorly characterized at the cellular level. The immediate structural consequences of the mechanical loading lead to a variety of inter-and intra-cellular signaling events that interact on multiple time and length scales. Thus, it is often difficult to establish cause-and-effect relationships such that appropriate treatment strategies can be devised. In this report, we showed that treating mechanically injured neuronal cells with an agent that promotes the resealing of disrupted plasma membranes rescues them from death at 24 h post-injury. A new in vitro model was developed to allow uniform mechanical loading conditions with precisely controlled magnitude and onset rate of loading. Injury severity increased monotonically with increasing peak shear stress and was strongly dependent on the rate of loading as assessed with the MTT cell viability assay, 24 h post-injury. Mechanical injury produced an immediate disruption of membrane integrity as indicated by a rapid and transient release of LDH. For the most severe injury, cell viability decreased approximately 40% with mechanical trauma compared to sham controls. Treatment of cells with Poloxamer 188 at 15 min post-injury restored long-term viability to control values. These data establish membrane integrity as a novel therapeutic target in the treatment of neuronal injury.

Effects of pluronic F68 micellization on the viability of neuronal cells in culture

“…8 Recently, it was demonstrated that F68 provided an acute recovery of axonal function in spinal cord injury models. 9,10 In fact, the treatment both restores membrane integrity acutely and restores viability of mechanically injured neuronal cells to control levels at 24 hours postinjury, 11 and both in vitro and in vivo studies have demonstrated the effectiveness of F68 in the recovery of damaged cell membranes. 9 Although these studies indicate the effectiveness of poloxamers as a pharmaceutical agent, little is known about the physicochemical mechanism that mediates molecular interactions between polymers and cells.…”

Poloxamer 188 Copolymer Membrane Sealant Rescues Toxicity of Amyloid Oligomers In Vitro

“…A number of other pathological conditions are also associated with lipid bilayer defects or damage, including membrane permeabilization in tissues exposed to ionizing radiation 23 or electrical shock, 24,25 myocardial tissues that accumulate lysophosphatidylcholine during ischemia, 26 traumatic brain injury, 27 and mechanical chaffing of the corneal epithelium. 28 In each of these examples, the compromise of cell membrane integrity has been reported to be restorable following injury by the sealing properties of poloxamer 188 (P188).…”

Combination Therapies for Traumatic Brain Injury – Prospective Considerations

“…Crush or weight drop models use an indenter to press on cultured tissue slices and reproduce contusion-type injuries (Sieg et al, 1999;Frantseva et al, 2002;Bendel et al, 2004). Fluid shear models induce cellular deformation with rotating fluid flow between two plates and are advantageous in that cells can be imaged during application of the fluid shear (LaPlaca and Thibault, 1997; Edwards et al, 2001;Serbest et al, 2005). In hydrostatic pressure models, cells or tissues are placed in a chamber which is pressurized, either with a transient pressure pulse (similar to a fluid percussion injury) or a tonic applied load (Panizzon et al, 1998;Etzion and Grossman, 2000;Panickar et al, 2002).…”