Autophagy is increased in mice after traumatic brain injury and is detectable in human brain after trauma and critical illness.
Autophagy is a homeostatic process for recycling of proteins and organelles, that increases during times of nutrient deprivation and is regulated by reactive oxygen species. We reported that autophagy can also be induced after traumatic brain injury (TBI) in mice.1 Specifically, autophagosomes and multilamellar bodies were frequently observed in cell processes and axons in injured brain regions by electron microscopy, and lipidated microtubule-associated protein light chain 3 (LC3-II), was increased after TBI vs. controls. To determine if antioxidants could reduce autophagy, separate mice were treated with the antioxidant ?-glutamylcysteinyl ethyl ester (GCEE). Treatment with GCEE preserved total antioxidant reserves, reduced LC3-II in injured brains, and improved both behavioral and histological outcome after TBI. Here we report that LC3-II and autophagosomes were detectable in brain tissue from humans after TBI. Taken together, we show that autophagy occurs after both experimental and clinical TBI, and that oxidative stress contributes to overall neuropathology after TBI in mice, at least in part by initiating or influencing autophagy.
Clark
Robert S B
RS
Department of Critical Care Medicine, the Safar Center for Resuscitation Research and the Brain Trauma Research Center, Pittsburgh, Pennsylvania 15260, USA. clarkrs@ccm.upmc.edu
Bayir
Hülya
H
Chu
Charleen T
CT
Alber
Sean M
SM
Kochanek
Patrick M
PM
Watkins
Simon C
SC
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology; D016638:Critical Illness; D004151:Dipeptides / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D004151:Dipeptides; C480860:Map1lc3b protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C067744:N-gamma-glutamylcysteine ethyl ester