Acute plasmalemma permeability and protracted clearance of injured cells after controlled cortical impact in mice.
Cell death after traumatic brain injury (TBI) evolves over days to weeks. Despite advances in understanding biochemical mechanisms that contribute to posttraumatic brain cell death, the time course of cell injury, death, and removal remains incompletely characterized in experimental TBI models. In a mouse controlled cortical impact (CCI) model, plasmalemma permeability to propidium iodide (PI) was an early and persistent feature of posttraumatic cellular injury in cortex and hippocampus. In cortical and hippocampal brain regions known to be vulnerable to traumatic cell death, the number of PI+ cells peaked early after CCI, and increased with increasing injury severity in hippocampus but not cortex (P<0.05). Propidium iodide labeling correlated strongly with hematoxylin and eosin staining in injured cells (r=0.99, P<0.001), suggesting that plasmalemma damage portends fatal cellular injury. Using PI pulse labeling to identify and follow the fate of a cohort of injured cells, we found that many PI+ cells recovered plasmalemma integrity by 24 h and were terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling negative, but nonetheless disappeared from injured brain by 7 days. Propidium iodide-positive cells in dentate gyrus showed significant ultrastructural damage, including plasmalemma and nuclear membrane damage or overt membrane loss, in all cells when examined by laser capture microdissection and transmission electron microscopy 1 to 24 h after CCI. The data suggest that plasmalemma damage is a fundamental marker of cellular injury after CCI; some injured cells might have an extended window for potential rescue by neuroprotective strategies.
Whalen
Michael J
MJ
Neuroscience Center, Massachusetts General Hospital, Charlestown, MA 02129, USA. MWhalen@Partners.org
Dalkara
Turgay
T
You
Zerong
Z
Qiu
Jianhua
J
Bermpohl
Daniela
D
Mehta
Niyati
N
Suter
Bernhard
B
Bhide
Pradeep G
PG
Lo
Eng H
EH
Ericsson
Maria
M
Moskowitz
Michael A
MA
D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D016923:Cell Death; D002463:Cell Membrane Permeability; D002540:Cerebral Cortex / Q000293:injuries / Q000473:pathology*; D006624:Hippocampus / Q000293:injuries / Q000473:pathology; D051379:Mice; D009685:Nuclear Envelope / Q000473:pathology; D011419:Propidium
D011419:Propidium
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