Polyethylene glycol (PEG), a non-toxic, ethylene oxide polymer, can reduce the behavioral complications associated with traumatic brain injury (TBI) when administered within four hours of the injury, according to a study published in the recent issue of the Journal of Biological Engineering.
Earlier researches had established that PEG spontaneously reassembles damaged plasmalemma by sealing the membrane and allowing the lipid core to resolve into each other, thereby reducing secondary axotomy. In order to assess the effect of PEG in limiting the behavioral symptoms following brain injury, Richard B Borgens, Professor of Developmental Anatomy at the Purdue University, Indiana, and coworkers, conducted the study by administering a single subcutaneous dose of PEG to rat models subjected to standardized brain injury. They also evaluated the consequences of delaying the PEG treatment by 2, 4 and 6 hours.
Computer managed open field behavioral test showed that the rat models treated within 2 hours of injury, exhibited a statistically significant behavioral improvement compared to controls. A delay in the PEG treatment by 4 hours showed a decline in behavioral performance when compared to the previous group. However, a 6-hour delay between the injury and treatment eliminated the beneficial effects of PEG injection. Based on the study findings, researchers suggested that PEG, like other acute treatments of trauma, could offer neuroprotection when administered at the earliest.
Borgens, et al. (Journal of Neuroscience Research, 2001) had earlier conducted a study, to evaluate the role of PEG in recovering damaged nerve membranes of the mammalian spinal cord, when administered through various routes. The team noted that a single subcutaneous administration of PEG (6 hours after the injury) to the spinal cord injured-adult guinea pig models, showed a rapid recovery in somatosensory-evoked potential (SSEP) conduction. It also significantly improved the cutaneous trunchi muscle (CTM) reflex, thereby restoring the conduction of nerve impulses across the injury site. Intravascularly injected PEG specifically targeted the hemorrhagic contusion in the injured spinal cord and was found to be safe. Based on these findings, the team suggested that parenteral administration of PEG could emerge as a potential, novel treatment modality for spinal and head injuries.
Polyethylene glycol has a wide range of clinical applications, apart from healing damaged motor neurons. Polyethylene glycol 3350, a class of osmotic laxatives, is used for the treatment of occasional constipation. Several animal studies have documented the protective role of dietary polyethylene glycol against colon carcinogenesis. Also, conjugation of PEG to proteins and drugs (PEGylation) is known to improve the pharmacodynamic and pharmacokinetic properties of the administered drug.
Traumatic brain injury or acquired brain injury is one of the common causes of major long-term disabilities in individuals surviving head injuries. Some of the leading causes of TBI include falls, motor vehicle accidents and assaults. Men have 1.5 times more risk than women in sustaining TBI, and African Americans have recorded a maximum death rate from TBI. According to the Centers for Disease Control and Prevention (CDC), approximately 1.4 million of the US population suffer from TBI annually, of which over 50,000 people die and more than 235,000 are hospitalized. It is also estimated that 5.3 million Americans currently have long-term disabilities that have threatened their capability of living independently.
The PEG-based novel pharmacological treatment aiding faster healing of damaged neurons could significantly reduce the long-term disabilities as well as family and financial burdens related to traumatic brain injury.
References
1. Koob AO, Colby JM, Borgens RB. Behavioral recovery from traumatic brain injury after membrane reconstruction using polyethylene glycol. J Biol Eng. 2008 Jun 27;2(1):9. [Epub ahead of print].
2. Borgens RB, Bohnert D. Rapid recovery from spinal cord injury after subcutaneously administered polyethylene glycol. J Neurosci Res. 2001 Dec 15;66(6):1179-86.
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