title: Acute plasmalemma permeability and protracted clearance of injured cells after controlled cortical impact in mice.
abstract: 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.
authors: Neuroscience Center, Massachusetts General Hospital, Charlestown, MA 02129, USA. MWhalen@Partners.org
authors: Michael J
authors: MJ
authors: Whalen
authors: Turgay
authors: T
authors: Dalkara
authors: Zerong
authors: Z
authors: You
authors: Jianhua
authors: J
authors: Qiu
authors: Daniela
authors: D
authors: Bermpohl
authors: Niyati
authors: N
authors: Mehta
authors: Bernhard
authors: B
authors: Suter
authors: Pradeep G
authors: PG
authors: Bhide
authors: Eng H
authors: EH
authors: Lo
authors: Maria
authors: M
authors: Ericsson
authors: Michael A
authors: MA
authors: Moskowitz
mesh_terms: 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
chemical_list: D011419:Propidium
references: J Neurotrauma. 1997 Apr;14(4):179-89
references: 9151767
references: Brain Res. 1996 Nov 11;739(1-2):111-9
references: 8955931
references: J Neurotrauma. 1997 Oct;14(10):715-27
references: 9383090
references: J Neurotrauma. 1999 Feb;16(2):109-22
references: 10098956
references: Exp Neurol. 1999 Jul;158(1):76-88
references: 10448419
references: J Cereb Blood Flow Metab. 2004 Oct;24(10):1119-32
references: 15529012
references: J Submicrosc Cytol Pathol. 2004 Apr;36(2):167-79
references: 15554503
references: Crit Care. 2005 Feb;9(1):66-75
references: 15693986
references: J Cell Biol. 2005 Feb 14;168(4):545-51
references: 15699214
references: J Neurotrauma. 2005 Feb;22(2):252-65
references: 15716631
references: J Submicrosc Cytol Pathol. 2004 Jul-Oct;36(3-4):273-83
references: 15906602
references: Nat Chem Biol. 2005 Jul;1(2):112-9
references: 16408008
references: FASEB J. 2006 Feb;20(2):308-10
references: 16371428
references: J Neurosci. 2006 Mar 22;26(12):3130-40
references: 16554464
references: J Cereb Blood Flow Metab. 2006 May;26(5):625-33
references: 16395279
references: J Neurotrauma. 2006 Aug;23(8):1241-53
references: 16928182
references: Biochim Biophys Acta. 2006 Sep-Oct;1757(9-10):1371-87
references: 16950166
references: J Cereb Blood Flow Metab. 2007 Nov;27(11):1806-18
references: 17406655
references: J Neurotrauma. 1999 Nov;16(11):1103-14
references: 10595826
references: J Neuropathol Exp Neurol. 2000 Aug;59(8):641-51
references: 10952055
references: J Neurochem. 2002 Jul;82(1):181-91
references: 12091479
references: Brain Res. 2003 Feb 28;964(2):264-78
references: 12576187
references: Am J Physiol Cell Physiol. 2003 May;284(5):C1309-18
references: 12676658
references: Cell Death Differ. 2003 Aug;10(8):928-9
references: 12868000
references: J Pharmacol Exp Ther. 2003 Oct;307(1):205-12
references: 12808000
references: Stroke. 2004 Jan;35(1):185-90
references: 14671239
references: J Neurosci. 2004 Apr 7;24(14):3543-53
references: 15071102
references: Brain Pathol. 2004 Apr;14(2):215-22
references: 15193035
references: Stroke. 2004 Sep;35(9):2189-94
references: 15256676
references: Acta Neuropathol. 1992;83(5):499-503
references: 1377858
references: J Neurotrauma. 1995 Apr;12(2):169-78
references: 7629863
references: Am J Pathol. 1995 Dec;147(6):1575-83
references: 7495282
references: Stroke. 1996 May;27(5):934-40
references: 8623116
references: J Neurosci. 1997 Nov 1;17(21):8106-17
references: 9334386