A new penumbra: transitioning from injury into repair after stroke

被引:459
作者
Lo, Eng H. [1 ,2 ]
机构
[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA 02129 USA
[2] Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA 02129 USA
关键词
D O I
10.1038/nm1735
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The penumbra is an area of brain tissue that is damaged but not yet dead after focal ischemia. The existence of a penumbra implies that therapeutic salvage is theoretically possible after stroke. The first decade of penumbral science investigated the ischemic regulation of electrophysiology, cerebral blood flow and metabolism. The second decade advanced our understanding of molecular mechanisms that mediate penumbral cell death. And the third decade saw the rapid development of clinical neuroimaging tools that are now increasingly applied in stroke patients. But how can we look ahead as we move into the fourth decade of penumbra research? This author speculates that a paradigm shift is needed. Most molecular targets for therapy have biphasic roles in stroke pathophysiology. During the acute phase, these targets mediate injury. During the recovery phase, the same mediators contribute to neurovascular remodeling. It is this boundary zone that comprises the new penumbra, and future investigations should dissect where, when and how damaged brain makes the transition from injury into repair.
引用
收藏
页码:497 / 500
页数:4
相关论文
共 51 条
[1]   Magnetic resonance imaging profiles predict clinical response to early reperfusion: The diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study [J].
Albers, Gregory W. ;
Thijs, Vincent N. ;
Wechsle, Lawrence ;
Kemp, Stephanie ;
Schlaug, Gottfried ;
Skalabrin, Elaine ;
Bammer, Roland ;
Kakuda, Wataru ;
Lansberg, Maarten G. ;
Shuaib, Ashfaq ;
Coplin, William ;
Hamilton, Scott ;
Moseley, Michael ;
Marks, Michael P. .
ANNALS OF NEUROLOGY, 2006, 60 (05) :508-517
[2]   N-methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke [J].
Arvidsson, A ;
Kokaia, Z ;
Lindvall, O .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2001, 14 (01) :10-18
[3]   CORTICAL EVOKED-POTENTIAL AND EXTRACELLULAR K+ AND H+ AT CRITICAL LEVELS OF BRAIN ISCHEMIA [J].
ASTRUP, J ;
SYMON, L ;
BRANSTON, NM ;
LASSEN, NA .
STROKE, 1977, 8 (01) :51-57
[4]   Mapping the ischaemic penumbra with PET: a new approach [J].
Baron, JC .
BRAIN, 2001, 124 :2-4
[5]   Brain response to injury and neurodegeneration - Endogenous neuroprotective signaling [J].
Bazan, NG ;
Marcheselli, VL ;
Cole-Edwards, K .
NEUROPROTECTIVE AGENTS, 2005, 1053 :137-147
[6]   A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia [J].
Borsello, T ;
Clarke, PGH ;
Hirt, L ;
Vercelli, A ;
Repici, M ;
Schorderet, DF ;
Bogousslavsky, J ;
Bonny, C .
NATURE MEDICINE, 2003, 9 (09) :1180-1186
[7]   Niaspan increases angiogenesis and improves functional recovery after stroke [J].
Chen, Jieli ;
Cui, Xu ;
Zacharek, Alex ;
Jiang, Hao ;
Roberts, Cynthia ;
Zhang, Chunling ;
Lu, Mei ;
Kapke, Alissa ;
Feldkamp, Carolyn S. ;
Chopp, Michael .
ANNALS OF NEUROLOGY, 2007, 62 (01) :49-58
[8]   Neurogenesis, angiogenesis, and MRI indices of functional recovery from stroke [J].
Chopp, Michael ;
Zhang, Zheng Gang ;
Jiang, Quan .
STROKE, 2007, 38 (02) :827-831
[9]   Multiple roles for MMPs and TIMPs in cerebral ischemia [J].
Cunningham, LA ;
Wetzel, M ;
Rosenberg, GA .
GLIA, 2005, 50 (04) :329-339
[10]   Pathobiology of ischaemic stroke: an integrated view [J].
Dirnagl, U ;
Iadecola, C ;
Moskowitz, MA .
TRENDS IN NEUROSCIENCES, 1999, 22 (09) :391-397