title: Hypoxia alters the expression of inhibitor of apoptosis proteins after brain trauma in the mouse.
abstract: Hypoxia worsens brain injury following trauma, but the mechanisms remain unclear. The purpose of this study was to determine the effect of traumatic brain injury (TBI) and secondary hypoxia (9% oxygen) on apoptosis-related protein expression, cell death, and behavior. Using a murine weight-drop model, TBI led to an early (6 h) increase followed by a later (24 h) decrease in neuronal apoptosis inhibitor protein (NAIP) expression in the olfactory and motor cortex; in contrast, TBI led to a sustained (6 h to 7 days) increase in NAIP in the striatum. The peak increase in the expression of NAIP (6-12 h) following TBI alone was delayed (1-7 days) when hypoxia was added to TBI. Hypoxia following TBI further depleted other apoptosis inhibitor proteins (IAPs) and activated caspases, as well as increased contusion size and worsened cell death. Hypoxia added to TBI also increased motor and feeding activity on days 2 and 4 compared to TBI alone. Hypoxia without TBI had no effect on the expression of IAPs or cell death. These findings show that IAPs have a potential role in the increased vulnerability of brain cells to hypoxia following TBI, and have implications for configuring future therapies for TBI.
authors: Division of Pediatric Emergency Medicine, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Angelo
authors: A
authors: Mikrogianakis
authors: Rachel E
authors: RE
authors: Shaye
authors: Phillip
authors: P
authors: Griffin
authors: Sarah
authors: S
authors: Kawesa
authors: Julia
authors: J
authors: Lockwood
authors: Nathalie H
authors: NH
authors: Gendron
authors: Isabelle
authors: I
authors: Gaboury
authors: Zul
authors: Z
authors: Merali
authors: Alex E
authors: AE
authors: Mackenzie
authors: James S
authors: JS
authors: Hutchison
mesh_terms: D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005247:Feeding Behavior; D000860:Hypoxia / Q000209:etiology* / Q000378:metabolism* / Q000523:psychology; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger