Polyethylene glycol treatment after traumatic brain injury reduces beta-amyloid precursor protein accumulation in degenerating axons.
Polyethylene glycol (PEG; 2,000 MW; 30% v/v) is a nontoxic molecule that can be injected intravenously and possesses well-documented neuroprotective properties in the spinal cord of the guinea pig. Recent studies have shown that intravenous PEG can also enter the rat brain parenchyma after injury and repair cellular membrane damage in the region of the corpus callosum. Disrupted anterograde axonal transport and resulting beta-amyloid precursor protein (APP) accumulation are byproducts of traumatic axonal injury (TAI) in the brain. APP accumulation indicates axonal degeneration as a result of axotomy, a detriment that can lead to cell death. In this study, we show that PEG treatment can eliminate APP accumulation in specific brain areas of rats receiving TAI. Six areas of the brain were analyzed: the medial cortex, hippocampus, lateral cortex, thalamus, medial lemniscus, and medial longitudinal fasciculus. Increased APP expression after injury was abolished in the thalamus and reduced in the medial longitudinal fasciculus by PEG treatment. In all remaining areas except for the lateral cortex, APP expression was not increased between injured and uninjured brains, indicating that damage was undetected in those brain areas in this study.
Center for Paralysis Research, Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana, USA.
Andrew O
AO
Koob
Richard B
RB
Borgens
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D020833:Diffuse Axonal Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D016896:Treatment Outcome
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents; D011092:Polyethylene Glycols