Polyethylene Glycol Protects Injured Neuronal Mitochondria

<i>Objective:</i> Polyethylene glycol (PEG), a hydrophilic polymer, can immediately repair neuronal membranes and inhibit free radical production following trauma. The aim of this study is to examine whether PEG can directly repair mitochondria in the event of trauma. <i>Method:</i> Purified brain mitochondria from guinea pigs were used. Mitochondrial function was assessed by biochemical methods and structural changes were observed by both fluorescence light microscopy and coherent anti-Stokes Raman scattering microscopy. <i>Results:</i> We present evidence suggesting that PEG is capable of directly reducing injury to mitochondria independent of plasma membrane repair. Specifically, the suppression of oxygen consumption rate of purified mitochondria due to H₂O₂ and/or calcium can be significantly reversed by 12.5 m<i>M</i> PEG. PEG also significantly reduced mitochondrial swelling due to similar injury. Furthermore, we have shown that such PEG-mediated mitochondrial protection is dependent on the molecular weight of PEG, suggesting a direct physical blockade of mitochondrial permeability transitional pore by PEG. <i>Conclusion:</i> These findings, coupled with previous evidence that PEG enters the cytosol following mechanical trauma, strongly indicate that there are at least 2 avenues of PEG-mediated cytoprotection in mechanically injured spinal cords: repair of plasma membrane and protection of mitochondria.