Hypoxia alters the expression of inhibitor of apoptosis proteins after brain trauma in the mouse.
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.
Mikrogianakis
Angelo
A
Division of Pediatric Emergency Medicine, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Shaye
Rachel E
RE
Griffin
Phillip
P
Kawesa
Sarah
S
Lockwood
Julia
J
Gendron
Nathalie H
NH
Gaboury
Isabelle
I
Merali
Zul
Z
Mackenzie
Alex E
AE
Hutchison
James S
JS
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
D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger